Molecular mechanisms and intervention approaches of heart failure (Review)
- Authors:
- Published online on: June 13, 2025 https://doi.org/10.3892/ijmm.2025.5566
- Article Number: 125
-
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
Introduction
There are >26 million individuals with heart failure worldwide (1). The incidence of heart failure increases with age and the prevalence of heart failure in patients >80 years of age is estimated to increase by 66% by 2030 (2,3). Heart failure is associated with high morbidity and >300,000 individuals die from heart failure each year worldwide, thus imposing a heavy medical burden on those affected (4-6). Heart failure is characterized by impaired ventricular filling or a decreased ejection fraction due to various pathological stimuli, such as high blood pressure, hyperglycemia, inflammatory factors and myocardial ischemia (7,8). In patients with heart failure, cardiac output cannot meet the metabolic needs of the body, which leads to insufficient blood perfusion of organs and tissues (9). Heart failure is the terminal stage of arrhythmia, dilated cardiomyopathy (DCM), hypertension, hypertrophic cardiomyopathy (HCM) and myocardial infarction (MI) (10). Therefore, studies on the molecular mechanisms through which the abovementioned cardiovascular diseases develop into heart failure will provide a solid basis for preventing heart failure.
The pathogenesis of heart failure is highly complex. The reported molecular mechanisms of heart failure mainly include the dysregulation of disease-related genes, noncoding RNAs, calcium ion homeostasis, mitochondrial homeostasis, cell apoptosis, extracellular matrix (ECM) remodeling, oxidative stress, the inflammatory response and the neuroendocrine system (11-22). Cardiac hypertrophy-related and fibrosis-related genes are associated with the occurrence and development of heart failure (23,24). The overexpression of cardiac hypertrophy-related genes, such as myosin binding protein C (MYBPC3) and myosin heavy chain 7 (MYH7), can lead to myocardial systolic and diastolic dysfunction (25,26). The expression of fibrosis-related genes such as transforming growth factor β1 (TGFB1) and actin α2 (ACTA2) can cause the activation and proliferation of myofibroblasts and the inflammatory response (27,28). The dysregulation of calcium ion homeostasis in myocardial cells also plays an important role in heart failure (17,18,29,30). The abnormal expression of microRNAs (miRNAs) is also associated with heart failure (14,15,31). miRNA-1 and miRNA-21 can regulate the expression of myocardial function-related genes and their dysregulation can disrupt the metabolism, apoptosis and contraction of myocardial cells (31-33). Mitochondrial dysfunction can disrupt the energy supply to myocardial cells, leading to impaired myocardial function (18,34). In addition, increased myocardial cell apoptosis and necroptosis are important risk factors for heart failure (19,35,36). Cardiomyocyte necroptosis can lead to cell swelling, cell membrane rupture and intracellular contents overflow, which together triggers inflammatory responses and heart failure (36-38). Previous studies have shown that inflammatory factors such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α) and excessive reactive oxygen species (ROS) can activate the intracellular apoptotic signaling pathway, which promotes myocardial cell death and heart failure (28,39-42). Inflammatory responses are closely linked with the occurrence and development of heart failure (43). The release of inflammatory factors such as TNF-α and IL-6 can promote an inflammatory cascade, which results in myocardial cell damage and cardiac fibrosis (21,43). Oxidative stress induced by excessive ROS production can cause myocardial damage and dysfunction, which leads to heart failure (20,41). Neuroendocrine system overactivation can also lead to heart failure (22). The abnormal activation of the renin-angiotensin-aldosterone system (RAAS) can increase angiotensin II (Ang II) levels, thus promoting myocardial remodeling (22,44). However, there are few effective preventive targets and therapeutic methods for treating heart failure due to its complex molecular mechanisms. Further studies on the detailed mechanisms of heart failure are highly important for the diagnosis, treatment and prevention of heart failure.
The present study reviewed recent research progress on the pathogenesis of heart failure, providing more references for further studies on the molecular mechanisms of heart failure and contributing to the development of potential therapeutic targets for heart failure.
Arrhythmia
Arrhythmia has a high mortality rate of ~10-15%; it is characterized by abnormalities in the frequency, rhythm, origin, conduction velocity and sequence of cardiac impulses (45-47). Arrhythmia can lead to insufficient heart pumping, damage the blood supply to various tissues and organs and result in dizziness, fatigue, amaurosis and syncope (46,48). Furthermore, long-term or severe arrhythmia can promote myocardial oxygen consumption, which gradually leads to myocardial remodeling and heart failure (49,50). It is important to investigate and reveal the pathogenesis of arrhythmia to prevent heart failure (51). However, the mechanisms by which arrhythmia causes heart failure are complex and remain to be fully elucidated.
Arrhythmia can result in heart failure through TGF-β1/Smad signaling, Wnt/β-catenin signaling and IL-1β secretion (Fig. 1) (52-54). The activation of TGF-β1/Smad signaling can cause cardiac fibrosis in atrial fibrillation, which leads to structural and functional damage to the heart and to heart failure (52). Smad2 and Smad3 are receptor-regulated Smads (R-Smads) that can be phosphorylated and activated by type I receptors of TGF-β (55,56). In addition, Smad4 is a comodulator Smad and Smad7 is a type of inhibitory Smad that can compete with R-Smads for binding to type I receptors of TGF-β and inhibit the phosphorylation of R-Smads (56,57). TGF-β1 expression is upregulated in arrhythmias; this increase decreases Smad7, weakens the competitiveness of Smad7 and promotes the activation of Smad2 and Smad3 (58,59). Activated Smad2 and Smad3 can form a complex with Smad4, and the complex can be transferred to the nucleus, upregulate the transcription of fibrosis-related genes, including collagen type I α1 chain (COL1A1), COL3A1, fibronectin 1 and ACTA2, and ultimately result in cardiac fibrosis (58,60-62). Another pathway is the classical Wnt pathway (53,63). Without Wnt stimulation, the 'destruction complex', which is composed of Axin, adenomatous polyposis coli protein, glycogen synthase kinase 3β and casein kinase 1α, is active in vivo (64). β-catenin is phosphorylated by the 'destruction complex', and phosphorylated β-catenin is ubiquitinated and then degraded by proteasomes, resulting in a low protein level of β-catenin in the cytoplasm (63,64). Once Wnt ligands bind to the Frizzled receptor and low-density lipoprotein receptor-related protein 5/6, the 'destruction complex' can be disrupted and scattered (65), protecting β-catenin from being phosphorylated and degraded, and thus promoting β-catenin accumulation (53,64). The accumulated β-catenin then enters the cell nucleus, interacts with T-cell factor/lymphoid enhancer factor to form a transcription activation complex, and upregulates the transcription of Wnt signaling-related genes, including ACTA2, connective tissue growth factor, COL1A1 and phosphoribosyl anthranilate isomerase 1, thus driving myocardial fibrosis (64,65). In the case of atrial fibrillation, the first and second pathways are abnormally activated, leading to myocardial fibrosis (66-69). Furthermore, as atrial fibrillation persists and atrial fibrosis progresses, the burden on the heart continues to increase, resulting in heart failure (69-71). In the third pathway, proinflammatory macrophages can induce atrial electrical remodeling by secreting IL-1β, which decreases the protein level of the atrial myocyte fibrillation protein Quaking (QKI) (54,72). Atrial fibrillation can induce proinflammatory macrophage polarization and IL-1β secretion from macrophages to downregulate QKI expression (72); it can reduce the binding of QKI and calcium voltage-gated channel subunit α1 C (CACNA1C) mRNA in atrial myocytes, which decreases the protein level of CACNA1C and L-type calcium currents (72,73). Ultimately, atrial fibrillation can induce electrical remodeling and affect cardiac function, which can cause heart failure in the long term (72-74).
There are numerous reported arrhythmia-targeted drugs, genes and surgical treatments for preventing heart failure (Table I) (75-81). In clinical practice, antiarrhythmic drugs include Class I, II, III and IV drugs (75,76). Class I sodium channel blockers can be divided into moderate sodium channel blockers (e.g., quinidine), mild blockers (e.g., lidocaine) and significant blockers (e.g., propafenone) (75,76); they can reduce the autonomy of myocardial cells to different degrees (75,76). Class II drugs, which are β-blockers (e.g., propranolol), can competitively block β adrenergic receptors to reduce myocardial autonomy; they are mainly used to treat sympathetic nervous system excitation-related arrhythmias (75,76). Class III drugs, which are potassium channel blockers (e.g., amiodarone), can prolong the action potential and refractory period of myocardial cells by blocking potassium channels; they are commonly used to treat structural heart disease-related arrhythmias (75,76). Class IV drugs, which are calcium channel blockers (e.g., verapamil), can act mainly on L-type calcium channels in myocardial cells and vascular smooth muscle cells (VSMCs), inhibit calcium ion influx and reduce the autonomy of the sinoatrial node (75,76); these drugs can improve myocardial electrophysiological stability and inhibit the myocardial damage induced by arrhythmia, which ultimately prevents heart failure (75,76). It has been reported that the insulin-like hormone relaxin can reverse TGFβ-induced cardiac fibrosis and increase the conduction velocity of atrial action to suppress arrhythmias (77,78). In addition, numerous genes have been reported to play important roles in the development of arrhythmia and may be prospective targets for preventing heart failure (74,79-81). MicroRNA (miR)-210-3p, a miRNA within extracellular vesicles derived from atrial myocytes, promotes atrial fibrosis by targeting the glycerol-3-phosphate dehydrogenase 1-like protein/phosphatidylinositol 3-kinase/AKT pathway. Therefore, miR-210-3p inhibitors can prevent Ang II-induced AF occurrence and persistence in rats, alleviate atrial fibrosis and prevent the development of heart failure (79). QKI can act as a prospective target for inhibiting electrical remodeling and heart failure (75) Surgical treatments include catheter ablation and left-ventricular assisted devices (80,81). Catheter ablation involves the use of radiofrequency currents, cryogenic energy or other energy sources to generate high or low temperatures locally, causing coagulation necrosis or cryogenic damage to abnormal myocardial tissue that leads to arrhythmia, thereby disrupting the conduction pathway or origin point of abnormal electrical activity, restoring normal cardiac rhythm, improving cardiac rhythm and pumping function, and thus playing a certain therapeutic role in heart failure (80). Left ventricular assistance devices use mechanical assistance to help the left ventricle pump blood out, increase cardiac output and improve systemic blood circulation; they are effective for treating arrhythmia and heart failure (81).
DCM
The five-year mortality rate for patients with DCM is ~20% (82). DCM is a type of primary cardiomyopathy and characterized by an enlarged heart and weakened myocardial contractility (83); it can cause dyspnea, fatigue, edema and other heart failure-related clinical symptoms (83,84). Finally, DCM can lead to heart failure (84). It is important to investigate the detailed mechanisms of DCM to prevent heart failure.
DCM can lead to heart failure through the activation of the rho-associated coiled-coil containing protein kinase 1 (ROCK1)-vimentin (VIM) pathway, an inflammatory cascade initiated by immune cells and calcium-independent receptor for α-latrotoxin (CFIRL)-mediated cardiac remodeling (Fig. 2) (85-87). The first pathway involves cytoskeleton regulation and mitochondrial autophagy (85). In DCM, mitochondrial dysfunction can activate the ROCK1-VIM pathway, leading to mitophagy (86). VIM can interact directly with mitochondria (85). Abnormally activated ROCK1 can accelerate the transport speed of damaged mitochondria by phosphorylating S72 of VIM, leading to the substantial accumulation of damaged mitochondria and significantly enhancing mitophagy (85,88). These effects result in insufficient mitochondrial energy supply and severely impaired myocardial contractility, causing heart failure (85). The second pathway involves immune cells and the inflammatory cascade (86,89). In DCM, immune cell activation leads to the development of associated inflammation (86). Among cardiomyocytes are macrophages, monocytes, B cells, T cells, natural killer (NK) cells, dendritic cells and granulocytes, and these immune cells secrete a variety of fibrotic mediators, such as cytokines, growth factors and stromal cell proteins, which play important roles in the occurrence and progression of myocardial fibrosis (86). Monocytes and macrophages can be transformed into myofibroblasts under the stimulation of various cytokines, resulting in the secretion of inflammatory mediators and fibrotic growth factors. Myeloid differentiation protein-2 can induce the proinflammatory state of monocytes in patients with DCM through toll-like receptor 4/nuclear factor-κB signaling, resulting in the secretion of monocyte chemotactic protein-1 to recruit monocytes to the site of inflammation to promote DCM progression and, concurrently, induce the expression of adhesion factors and the secretion of IL-6 and IL-1β by monocytes (86,89). Elevated levels of IL-6 and IL-1β in patients with DCM may lead to cardiomyocyte apoptosis and impaired systolic function of the heart (89). Cardiac macrophages can be divided into two types, C-C motif chemokine receptor 2 (CCR)2+ and CCR2−, on the basis of the protein level of CCR2 (86). CCR2+ macrophages are involved in cardiac fibrosis and inflammatory responses, whereas CCR2− macrophages mediate tissue repair (86). CCR2+ macrophages in DCM can recruit monocytes and neutrophils to the inflammatory area by secreting inflammatory cytokines and chemokines, which promote the inflammatory response (86). B cells can secrete a variety of cytokines, including proinflammatory agents (e.g., TNF-α) and anti-inflammatory molecules (e.g., IL-1) (87). Patients with DCM have increased TNF-α and decreased IL-1 secreted by B cells, which impairs their anti-inflammatory ability (86). T cells can be divided into T helper 1 (Th1) cells, Th22 cells, Th17 cells, T follicular helper cells and regulatory T cells and are involved in cardiac inflammation and injury, which play crucial roles in the development of DCM (86). NK cells are important anti-inflammatory cells and their depletion can cause DCM and heart failure (86). The inflammatory cascade caused by various immune cells can eventually lead to cardiac fibrosis and heart failure (86). The third pathway is CFIRL-mediated cardiac remodeling (87). In DCM, significantly upregulated CFIRL expression stimulated by pressure overload or Ang II can recruit enolase 1 to the nucleus to form a transcription activation complex that promotes IL6 gene transcription (87). The abnormal upregulation of IL-6 expression mediated by CFIRL has an autocrine effect, directly promoting the proliferation and differentiation of myofibroblasts and indirectly stimulating cardiac hypertrophy, which ultimately leads to heart failure (87).
Previous studies have reported numerous DCM-targeted drugs, genes and surgical treatments for preventing heart failure (Table I) (83,86,87,90-98). Immunotherapy is an important intervention approach for preventing DCM and heart failure (86,90). Immunotherapy can regulate the immune system and suppress the myocardial damage caused by autoimmune reactions (86); it includes immunosuppressive therapy, intravenous immunoglobulin and immunoadsorption (86). During the clinical trial stage, immunosuppressive therapy (e.g., prednisolone and azathioprine) can reduce the antibody immune response by inhibiting the activity of immune response-related cells such as T cells, B cells and macrophages (86). Intravenous immunoglobulin can recognize and bind to dysregulated antibodies in patients, which reduces the attack and damage caused by dysregulated antibodies on myocardial cells (86). In immune adsorption therapy, extracorporeal circulation is used to selectively remove dysregulated antibodies, immune complexes and other related immune active substances from the blood using an immune adsorption column (86,90). Angiotensin-converting enzyme inhibitors (ACEIs) can effectively prevent cardiac fibrosis in DCM and the development of heart failure (91). β-blockers can reverse left ventricular dilation, which protects cardiac function and heart failure (92,93). Mineralocorticoid receptor antagonists, which can increase the ejection fraction in and reduce the mortality rate of patients with heart failure, are used to treat DCM (83,94). In addition, certain genes have been reported to play important roles in DCM and may be prospective targets for preventing heart failure (87,95). DCM is a typical hereditary cardiomyopathy and gene therapy can be used to replace diseased genes (95). The dysregulation of sarcomere-related genes [e.g., titin, troponin T2 (TNNT2) and TNNC1] is the main cause of DCM (95). By replacing these dysregulated genes, DCM can be used to intervene in the development of heart failure (95). A significant increase in CFIRL can mediate cardiac remodeling; therefore, CFIRL can serve as a potential therapeutic target (87). For surgical treatment, nonischemic DCM can be treated with a left ventricular assist device to reverse left ventricular remodeling and prevent progression to heart failure (96,97). Intra-aortic balloon pump catheters are used as a bridge to heart transplantation and a transitional therapy for patients with advanced heart failure (98).
Hypertension
Over the past 30 years, ~8.5 million individuals have died worldwide from hypertension (99). Hypertension is characterized by increased pressure overload of the heart and its long-term development can further enlarge the left ventricle, increase myocardial oxygen consumption, induce weakened myocardial contractility and reduce cardiac output, which eventually results in heart failure (100). It is essential to study the molecular mechanisms of hypertension and intervene in its development to prevent heart failure.
Vascular remodeling is an important pathway through which hypertension leads to heart failure (101). Vascular remodeling is a type of pathological change that is difficult to reverse (101). Key events in vascular remodeling include endothelial cell (EC) dysfunction, the migration and proliferation of VSMCs and changes in the collagen ECM (Fig. 3) (101,102). Hypertension is an important risk factor for EC dysfunction (102). EC dysfunction resulting from insufficient nitric oxide production and increased levels of ROS in blood vessels can lead to a decreased vasodilation capacity, which causes the blood vessels to narrow and blood pressure to continue to rise, eventually leading to vascular remodeling and heart failure (102,103). Hypertension is closely related to the contractile function of VSMCs (101). The phenotypic conversion of VSMCs from a contractile to a synthetic phenotype causes vascular calcification and the proliferation and migration of VSMCs due to the overproduction of Ang II in patients with hypertension, which leads to impaired vascular contraction function and heart failure (99,101,104). Alterations in the ECM are currently irreversible pathological changes in hypertension (101). The dysregulated synthesis of the ECM, such as increased collagen and decreased elastin synthesis, is caused by the activation of matrix metalloproteinases and the deposition of advanced glycation end products in hypertension, which can increase the hardness and weaken the elasticity of the vascular wall (101).
In addition, hypertension can cause heart failure through cardiac remodeling (105). Cardiac remodeling is a physiological adaptation to chronic pressure overload (106). Key events in cardiac remodeling include cardiomyocyte hypertrophy and myocardial fibrosis (Fig. 3) (107-109). Myocardial cell hypertrophy is an early adaptive change in the heart to hypertension (110). Myocardial cells are stimulated by mechanical traction and abnormalities in Ang II, norepinephrine and calcium regulation, which cause the compensatory hypertrophy of myocardial cells, promoting cardiac remodeling and heart failure (110,111). Long-term hypertension causes cardiac fibroblasts to transform into myofibroblasts, which secrete large amounts of type I and type III collagen, leading to excessive deposition of ECM and the gradual development of myocardial fibrosis (112,113). The infiltration of inflammatory cells, the release of inflammatory factors and the stimulation of Ang II promote myocardial fibrosis, leading to increased myocardial stiffness, limited cardiac diastolic function and ultimately heart failure (113,114).
Numerous hypertension-targeted drugs for preventing heart failure have been reported (Table I) (115-120). The acetyltransferase p300 inhibitor L002 can prevent the progression of heart failure by reversing hypertension-induced myocardial fibrosis and left ventricular hypertrophy (115). Lipoprotein-associated phospholipase A2 plays a key role in hypertensive cardiac fibrosis, and its inhibitor, darapladib, can prevent Ang II-induced cardiac remodeling and inflammation (116). Voltage-gated L-type Ca2+ channel blockersincluding dihydropyridines (e.g., amlodipine), phenylalkylamines (e.g., verapamil) and benzothiazepines (e.g., diltiazem), are mainly used to treat hypertension (117). The ROS produced by nicotinamide adenine dinucleotide phosphate oxidase (NOX) activation can induce the dysfunction of other oxidase systems, which leads to a vicious cycle and exacerbates cardiovascular tissue damage (118). Novel NOX inhibitors, such as GKT137831 and GSK2795039, have increased selectivity and specificity for alleviating oxidative stress (118). In a mouse model, NOX inhibitors have been shown to have inhibitory effects on ROS production, which implies that these inhibitors have the ability to suppress cardiac remodeling and heart failure (118). In addition, there are several clinically recommended antihypertensive drugs, including the RAAS blockers, ACEIs, angiotensin receptor blockers, calcium channel blockers and thiazides or thiazide diuretics (119,120).
HCM
The prevalence of HCM, which is influenced by genetic factors and sarcomere mutations, is 1:200 (121,122). HCM is characterized by myocardial hypertrophy, especially asymmetric thickening of the ventricular septum (123). This abnormal myocardial hypertrophy can reduce the size of the heart chambers and severely impair cardiac diastolic function, which leads to hemodynamic dysregulation (123). Long-term hemodynamic dysregulations can gradually fatigue the heart and eventually contribute to heart failure (124). It is important to investigate the molecular mechanisms of HCM further, to identify more potential targets for developing therapeutic options for heart failure.
Mutations in sarcomere-related genes, including MYH7, MYBPC3, TNNT2, TNNI3 and tropomyosin 1 (TPM1), have been shown to lead to HCM and heart failure (Fig. 4) (123,124). These mutated sarcomere-related genes can impair the contraction, relaxation and energy metabolism of myocardial cells, potentially triggering the occurrence and development of HCM and heart failure (13). Mutations in MYH7 may disrupt normal myosin head structure and function, thus damaging myocardial contractility (125). The cMyBPC truncation mutant of the MYBPC3 gene increases the proportion of myosin in the more active DRX conformation through a haploinsufficiency mechanism, ultimately driving excessive contraction, impairing relaxation and increasing energy expenditure (25,126). Mutations in TNNT2 can hinder the interaction of TNNT with calcium ions, thus disrupting calcium ion dynamics and the contraction and relaxation rhythm in myocardial cells (127). Mutations in TNNI3 can weaken the inhibitory effect of TNNI3 on the actin-myosin interaction, which results in insufficient relaxation during diastole (128). Mutations in TPM1 can induce the spiral structure of α-TPM to become distorted or destroyed, which destabilizes actin filaments and damages myocardial systolic and diastolic function (129).
There are numerous reported HCM-targeted drugs, genes and surgical treatments for preventing heart failure (Table I) (130-133). In clinical practice, the β-adrenergic antagonists verapamil and disopyramide are mainly used to treat HCM (130). Sarcomere contractile inhibitors can prevent heart failure by reducing myofilament sensitivity to calcium ions or directly inhibiting myosin to weaken myocardial contractile function (131). For instance, aficamten can decrease myosin ATPase activity and the interaction of myosin with actin, which reduces cardiac contractility (131); it has been reported to exhibit an inhibitory effect on cardiac contractility and good pharmacokinetic properties in healthy animals and HCM models (132). Currently, phase III clinical trials are underway (132). Gene therapy is highly important for treating HCM (133). Exploring various genetic mutation sites to identify exon methylation and miRNA levels in HCM is beneficial for the development of gene-targeted therapy methods (133). For instance, in male patients with HCM with MYBPC3 gene GAGT deletion, the successful repair of germline mutations was achieved, which improved homologous-directed repair efficiency without off-target events (133). Alcohol septal ablation and surgical myectomy are the primary surgical treatments used (131).
MI
Until 2019, MI accounted for 49.2% of deaths caused by CVD; additionally, MI has attracted widespread attention because of its high mortality rate (134). MI is characterized by myocardial ischemia due to atherosclerosis, which impairs cardiac contraction and relaxation and ultimately leads to heart failure (135,136). Studying the detailed mechanisms of MI will be beneficial for the development of potential treatment approaches for heart failure (137).
MI can result in heart failure through the regulation of cell death, including apoptosis, Ang II-induced necroptosis, mitochondrial homeostasis and Ca2+ transients (138-146). The first major pathway is cell death (Fig. 5). Previous studies have shown that solute carrier family 40 member 1 and steap family member 4 expression is upregulated in MI, which promotes iron efflux (138). More divalent iron ions are transported extracellularly, which causes iron deficiency in cells and myocardial mitochondrial dysfunction because electron transfer within mitochondria requires significant amounts of iron ions (138,139). Myocardial mitochondrial dysfunction leads to insufficient energy generation, disrupts the intracellular redox balance (e.g., NADPH/NADH levels), and promotes the production of ROS and oxidative stress, which ultimately stimulates myocardial cell apoptosis (Fig. 5) (138,140). In addition, Ang II-induced necroptosis plays an important role in the transition from MI to heart failure (Fig. 5) (141). In acute MI, Ang II levels are significantly elevated. Ang II is one of the main neurohumoral factors resulting in the development of heart failure (141). Ang II is involved in myocardial cell necroptosis by promoting the release of humoral factors from cardiac fibroblasts (141). Necroptosis promotes cell rupture and the release of intracellular contents, such as damage-associated molecular patterns and lactate dehydrogenase, which stimulate an inflammatory response and ultimately trigger heart failure (141,142). In MI, mitochondrial dysfunction, mitochondrial morphological swelling and reduced cristae can lead to energy metabolism disorders and an insufficient cellular energy supply (143). Dysfunction of the mitochondrial electron transport chain in MI can result in the excessive production of ROS (143). Excessive ROS can attack mitochondrial membranes, proteins and DNA, which causes mitochondrial damage (143). The opening of the mitochondrial permeability transition pore in MI can result in abnormalities in the mitochondrial membrane potential, the cessation of ATP synthesis and the release of proinflammatory factors (e.g., cytochrome C) into the cytoplasm, which initiates cell apoptosis (143). Calcium transients are another important mechanism of MI (144). Changes in the calcium concentration significantly affect myocardial cells (144,145). A decrease in the amplitude of calcium transients can weaken the contractility of myocardial cells and affect the blood pumping function of the heart (145,146). A prolonged duration of calcium transients can hinder the reduction in the intracellular calcium concentration during diastole, which impairs diastolic function and limits cardiac filling (17,145).
There are numerous reported MI-targeted drugs and surgical treatments for preventing heart failure (Table I) (147-153). In clinical practice, MI-targeted drugs include ACEIs (e.g., ramipril and perindopril), P2Y12 receptor inhibitors (e.g., clopidogrel) and statins (e.g., atorvastatin, simvastatin and rosuvastatin) (147). ACEIs can improve endothelial function and reduce peripheral vascular resistance in the heart (147). They can reduce blood clots and the burden on the heart to intervene in heart failure (148). P2Y12 receptor antagonists can inhibit platelet aggregation to reduce thrombosis and prevent myocardial ischemic necrosis and heart failure (149). Dual antiplatelet therapy comprises aspirin and a P2Y receptor antagonist, which has always been used to treat acute MI (149); it can protect patients with acute MI from developing heart failure by reducing the degree of systemic atherothrombosis (149,150). Statins can lower blood lipid levels, particularly the synthesis of low-density lipoprotein cholesterol, which reduces blood lipid levels and prevents plaque formation (151). In stem cell therapy, differentiated new cardiomyocytes can be used to replace cardiomyocytes damaged during MI, thus inhibiting cell apoptosis and heart failure (152). Coronary intervention can effectively clear up occluded coronary arteries, which increases myocardial blood supply and prevents heart failure (153).
Other CVDs
Other CVDs, including doxorubicin-induced cardiomyopathy, iron overload cardiomyopathy, sepsis cardiomyopathy, viral myocarditis and diabetic cardiomyopathy, can also develop into heart failure at the end stage (154-162). Doxorubicin-induced cardiomyopathy can result in heart failure through oxidative stress injury, apoptosis and mitochondrial damage (154,155). The development of inflammation, cardiac hypertrophy and fibrosis are the main pathways through which iron overload cardiomyopathy leads to heart failure (156,157). heart failure is caused primarily by inflammatory responses in sepsis cardiomyopathy (158). In viral myocarditis, heart failure mainly results from direct injury and immune-mediated injury pathways (159,160). Diabetic cardiomyopathy can result in heart failure through autonomic dysfunction, cardiac hypertrophy and fibrosis (161,162). However, the detailed mechanisms of the abovementioned CVDs remain to be elucidated.
Conclusion and perspective
The five-year mortality rate of patients with heart failure is estimated to be ~50% worldwide (163). The pathological mechanisms of heart failure include cardiac fibrosis, cardiac hypertrophy, cardiomyocyte death, cardiac sarcomere disorders, mitochondrial dysfunction and vascular remodeling (110,132,143,164-172). Intervention approaches for suppressing the progression of heart failure are available at both the experimental and clinical stages. However, these approaches have many challenges and limitations, including off-target effects, side effects and poor translation of basic research into clinical practice (173). Gene therapies, which mainly consist of gene editing technology and noncoding nucleotide acid methods, can be used to prevent and treat heart failure (174,175). Gene editing technology can be used to replace dysregulated sarcomere proteins by targeting related genes (174). CRISPR-Cas9 may be used as 'gene scissors' that can remove erroneous gene fragments and restore related normal genes. The RNA-guided adeno-associated virus 9 delivery of effective Cas9 nucleases can inactivate pathogenic mutant genes in HCM, thereby preventing the progression of heart failure (176). In addition, the discovery and application of regulatory RNA have attracted increasing attention in medical research. Ambrose and Rufkun were awarded the Nobel Prize in Physiology or Medicine in 2024 for their discovery of the miRNA-Lin-14 (177). miR-133, a type of noncoding nucleotide acid, can alleviate heart failure by downregulating the expression of proapoptotic proteins such as caspases-3 and Bax and reducing cardiomyocyte apoptosis (175). However, the main technical problem and challenge are off-target risks, which may cause other genetic abnormalities (174). Drug therapies for heart failure have side effects, including dry cough caused by ACEIs, slow movement and low blood pressure caused by β-blockers, and electrolyte imbalance caused by diuretics (178-180). In addition, it has been reported that human fibroblasts can be reprogrammed into induced cardiac-like myocytes to regenerate cardiomyocytes and prevent MI in the experimental stage; however, further studies are needed to promote their translation into clinical practice (152).
There are reported methods and strategies to address the abovementioned issues. Nanotechnology can improve the precise targeting and reduce off-target effects; it can be used to package and deliver drugs to the target site of related CVDs accurately, which thereby reduces off-target effects (181,182). The integration of traditional Chinese and Western medicine can diminish drug side effects (183-189). Previous studies have shown that Platycodon grandiflorum and Flos Farfarae can alleviate the dry cough caused by ACEIs, and that ginseng can ameliorate the bradycardia and hypotension caused by β-blockers (184-187). Specific traditional Chinese medicine active components, such as glycyrrhizic acid and ginsenoside, can protect patients from the adverse effects of Western medicine (188,189). In addition, clinical translation requires more in-depth clinical trials.
Current cutting-edge research technologies, such as superresolution fluorescence microscopy, cryo-electron microscopy and photoelectric coupling technology, can promote research on heart failure and lay the foundation for drug development (190-192). In addition, nanotechnology and noncoding RNA technology can improve the precise targeting of disease treatments (176,182). The present review provides references for basic research on heart failure and lays a theoretical foundation for the development of therapeutic drugs.
Availability of data and materials
Not applicable.
Authors' contributions
All of the authors contributed to the manuscript. SG, YH and ZR drafted the manuscript, and LL, ZY, LW, XY, ML and XG performed the literature search. SG, YH, LL, ZY, LW, XY, ML and XG edited the manuscript. ZR conceived the study and edited and finalized the manuscript. All authors have read and confirmed the final version of the manuscript. Data authentication is not applicable.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Acknowledgments
The authors thank Dr Zhanhong Ren (Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Hubei University of Science and Technology, Xianning, China) for contributing ideas and editing the manuscript and Miss Yingqing Hu, Miss Li Ling, Mr. Zhuangzhuang Yang, Miss Luxuan Wan (School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, China) and Miss Shuang Guo, Dr Xiaosong Yang, Dr Min Lei and Dr Xiying Guo (Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Hubei University of Science and Technology, Xianning, China) for editing the manuscript. Figures were created and designed by Figdraw.
Funding
This study was jointly supported by Hubei Provincial Natural Science Foundation and Xianning of China (grant no. 2025AFD407), the Special Project on Diabetes and Angiopathy (grant no. 2024TNB04), the Scientific Research and Innovation Team of Hubei University of Science and Technology (grant no. 2022T01) and the Horizontal Scientific Research Project of Hubei University of Science and Technology (grant no. 2024HX132).
References
|
Ketabi M, Andishgar A, Fereidouni Z, Sani MM, Abdollahi A, Vali M, Alkamel A and Tabrizi R: Predicting the risk of mortality and rehospitalization in heart failure patients: A retrospective cohort study by machine learning approach. Clin Cardiol. 47:e242392024. View Article : Google Scholar : PubMed/NCBI | |
|
Xu X and Xu Z; Association between phenotypic age the risk of mortality in patients with heart failure: A retrospective cohort study. Clin Cardiol. 47:e243212024. View Article : Google Scholar | |
|
Pratley R, Guan X, Moro RJ and do Lago R: Chapter 1: The burden of heart failure. Am J Med. 137(2S): S3–S8. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Mulugeta H, Sinclair PM and Wilson A: Prevalence of depression and its association with health-related quality of life in people with heart failure in low- and middle-income countries: A systematic review and meta-analysis. PLoS One. 18:e02831462023. View Article : Google Scholar : PubMed/NCBI | |
|
Shahim B, Kapelios CJ, Savarese G and Lund LH: Global public health burden of heart failure: An updated review. Card Fail Rev. 9:e112023. View Article : Google Scholar : PubMed/NCBI | |
|
Emmons-Bell S, Johnson C and Roth G: Prevalence, incidence and survival of heart failure: A systematic review. Heart. 108:1351–1360. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Caturano A, Vetrano E, Galiero R, Salvatore T, Docimo G, Epifani R, Alfano M, Sardu C, Marfella R, Rinaldi L and Sasso FC: Cardiac hypertrophy: From pathophysiological mechanisms to heart failure development. Rev Cardiovasc Med. 23:1652022. View Article : Google Scholar : PubMed/NCBI | |
|
Castiglione V, Aimo A, Vergaro G, Saccaro L, Passino C and Emdin M: Biomarkers for the diagnosis and management of heart failure. Heart Fail Rev. 27:625–643. 2022. View Article : Google Scholar : | |
|
Bozkurt B, Coats AJS, Tsutsui H, Abdelhamid CM, Adamopoulos S, Albert N, Anker SD, Atherton J, Böhm M, Butler J, et al: Universal definition and classification of heart failure: A report of the heart failure society of America, heart failure association of the European society of cardiology, Japanese heart failure society and writing committee of the universal definition of heart failure: Endorsed by the Canadian heart failure society, heart failure association of India, cardiac society of Australia and New Zealand, and Chinese heart failure association. Eur J Heart Fail. 23:352–380. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Triposkiadis F, Xanthopoulos A, Parissis J, Butler J and Farmakis D: Pathogenesis of chronic heart failure: Cardiovascular aging, risk factors, comorbidities, and disease modifiers. Heart Fail Rev. 27:337–344. 2022. View Article : Google Scholar | |
|
Huang K, Wu H, Xu X, Wu L, Li Q and Han L: Identification of TGF-β-related genes in cardiac hypertrophy and heart failure based on single cell RNA sequencing. Aging (Albany NY). 15:7187–7218. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Gu JJ, Du TJ, Zhang LN, Zhou J, Gu X and Zhu Y: Identification of ferroptosis-related genes in heart failure induced by transverse aortic constriction. J Inflamm Res. 16:4899–4912. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Marian AJ: Molecular genetic basis of hypertrophic cardiomyopathy. Circ Res. 128:1533–1553. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Madè A, Bibi A, Garcia-Manteiga JM, Tascini AS, Piella SN, Tikhomirov R, Voellenkle C, Gaetano C, Leszek P, Castelvecchio S, et al: circRNA-miRNA-mRNA deregulated network in ischemic heart failure patients. Cells. 12:25782023. View Article : Google Scholar : PubMed/NCBI | |
|
Wong LL, Wang J, Liew OW, Richards AM and Chen YT: MicroRNA and heart failure. Int J Mol Sci. 17:5022016. View Article : Google Scholar : PubMed/NCBI | |
|
Park JH and Kho C: MicroRNAs and calcium signaling in heart disease. Int J Mol Sci. 22:105822021. View Article : Google Scholar : PubMed/NCBI | |
|
Saad NS, Mashali MA, Repas SJ and Janssen PML: Altering calcium sensitivity in heart failure: A crossroads of disease etiology and therapeutic innovation. Int J Mol Sci. 24:175772023. View Article : Google Scholar : PubMed/NCBI | |
|
Hinton A Jr, Claypool SM, Neikirk K, Senoo N, Wanjalla CN, Kirabo A and Williams CR: Mitochondrial structure and function in human heart failure. Circ Res. 135:372–396. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Xue P, Liu Y, Wang H, Huang J and Luo M: miRNA-103-3p-Hlf regulates apoptosis and autophagy by targeting hepatic leukaemia factor in heart failure. ESC Heart Fail. 10:3038–3045. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Pagan LU, Gomes MJ, Martinez PF and Okoshi MP: Oxidative stress and heart failure: Mechanisms, signalling pathways, and therapeutics. Oxid Med Cell Longev. 2022:98295052022. View Article : Google Scholar : PubMed/NCBI | |
|
Hanna A and Frangogiannis NG: Inflammatory cytokines and chemokines as therapeutic targets in heart failure. Cardiovasc Drugs Ther. 34:849–863. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Manolis AA, Manolis TA and Manolis AS: Neurohumoral activation in heart failure. Int J Mol Sci. 24:154722023. View Article : Google Scholar : PubMed/NCBI | |
|
Cappola TP and Burke MF: Studying Heart failure through the lens of gene regulation. Circ Heart Fail. 13:e0076472020. View Article : Google Scholar : PubMed/NCBI | |
|
Levin MG, Tsao NL, Singhal P, Liu C, Vy HMT, Paranjpe I, Backman JD, Bellomo TR, Bone WP, Biddinger KJ, et al: Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure. Nat Commun. 13:69142022. View Article : Google Scholar : PubMed/NCBI | |
|
Tudurachi BS, Zăvoi A, Leonte A, Țăpoi L, Ureche C, Bîrgoan SG, Chiuariu T, Anghel L, Radu R, Sascău RA and Stătescu C: An update on MYBPC3 gene mutation in hypertrophic cardiomyopathy. Int J Mol Sci. 24:105102023. View Article : Google Scholar : PubMed/NCBI | |
|
Park J, Packard EA, Levin MG, Judy RL; Regeneron Genetics Center; Damrauer SM, Day SM, Ritchie MD and Rader DJ: A genome-first approach to rare variants in hypertrophic cardiomyopathy genes MYBPC3 and MYH7 in a medical biobank. Hum Mol Genet. 31:827–837. 2022. View Article : Google Scholar : | |
|
Akboua H, Eghbalzadeh K, Keser U, Wahlers T and Paunel-Görgülü A: Impaired non-canonical transforming growth factor-β signalling prevents profibrotic phenotypes in cultured peptidylarginine deiminase 4-deficient murine cardiac fibroblasts. J Cell Mol Med. 25:9674–9684. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Qian L, Xu H, Yuan R, Yun W and Ma Y: Formononetin ameliorates isoproterenol induced cardiac fibrosis through improving mitochondrial dysfunction. Biomed Pharmacother. 170:1160002024. View Article : Google Scholar | |
|
Roe AT, Frisk M and Louch WE: Targeting cardiomyocyte Ca2+ homeostasis in heart failure. Curr Pharm Des. 21:431–448. 2015. View Article : Google Scholar : | |
|
Shah K, Seeley S, Schulz C, Fisher J and Gururaja Rao S: Calcium channels in the heart: Disease states and drugs. Cells. 11:9432022. View Article : Google Scholar : PubMed/NCBI | |
|
Al-Hayali MA, Sozer V, Durmus S, Erdenen F, Altunoglu E, Gelisgen R, Atukeren P, Atak PG and Uzun H: Clinical value of circulating microribonucleic acids miR-1 and miR-21 in evaluating the diagnosis of acute heart failure in asymptomatic type 2 diabetic patients. Biomolecules. 9:1932019. View Article : Google Scholar : PubMed/NCBI | |
|
Vilella-Figuerola A, Gallinat A, Escate R, Mirabet S, Padró T and Badimon L: Systems biology in chronic heart failure-identification of potential miRNA regulators. Int J Mol Sci. 23:152262022. View Article : Google Scholar : PubMed/NCBI | |
|
Xu R, Wu J, Yang CJ, Kang L, Ji YY, Li C, Ding ZW and Zou YZ: A circRNA-miRNA-mRNA network analysis underlying pathogenesis of human heart failure. J Geriatr Cardiol. 20:350–360. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Gallo G, Rubattu S and Volpe M: Mitochondrial dysfunction in heart failure: From Pathophysiological mechanisms to therapeutic opportunities. Int J Mol Sci. 25:26672024. View Article : Google Scholar : PubMed/NCBI | |
|
van Empel VPM, Bertrand ATA, Hofstra L, Crijns HJ, Doevendans PA and De Windt LJ: Myocyte apoptosis in heart failure. Cardiovasc Res. 67:21–29. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Guo X, Chen Y and Liu Q: Necroptosis in heart disease: Molecular mechanisms and therapeutic implications. J Mol Cell Cardiol. 169:74–83. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Kang Y and Wang Q: Potential therapeutic value of necroptosis inhibitor for the treatment of COVID-19. Eur J Med Res. 27:2832022. View Article : Google Scholar : PubMed/NCBI | |
|
Lu LQ, Tian J, Luo XJ and Peng J: Targeting the pathways of regulated necrosis: A potential strategy for alleviation of cardio-cerebrovascular injury. Cell Mol Life Sci. 78:63–78. 2021. View Article : Google Scholar | |
|
Zhang H and Dhalla NS: The role of pro-inflammatory cytokines in the pathogenesis of cardiovascular disease. Int J Mol Sci. 25:10822024. View Article : Google Scholar : PubMed/NCBI | |
|
Bishopric NH, Andreka P, Slepak T and Webster KA: Molecular mechanisms of apoptosis in the cardiac myocyte. Curr Opin Pharmacol. 1:141–150. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Tsutsui H, Kinugawa S and Matsushima S: Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol. 301:H2181–H2190. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Khoynezhad A, Jalali Z and Tortolani AJ: A synopsis of research in cardiac apoptosis and its application to congestive heart failure. Tex Heart Inst J. 34:352–359. 2007.PubMed/NCBI | |
|
Paulus WJ and Zile MR: From systemic inflammation to myocardial fibrosis: The heart failure with preserved ejection fraction paradigm revisited. Circ Res. 128:1451–1467. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Kjaer A and Hesse B: Heart failure and neuroendocrine activation: Diagnostic, prognostic and therapeutic perspectives. Clin Physiol. 21:661–672. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Blackwell DJ, Schmeckpeper J and Knollmann BC: Animal models to study cardiac arrhythmias. Circ Res. 130:1926–1964. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Reißmann B, Rottner L, Rillig A and Metzner A: Cardiac arrhythmia. MMW Fortschr Med. 163:62–71. 2021.In German. View Article : Google Scholar | |
|
Fu DG: Cardiac arrhythmias: Diagnosis, symptoms, and treatments. Cell Biochem Biophys. 73:291–296. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Paludan-Müller C, Vad OB, Stampe NK, Diederichsen SZ, Andreasen L, Monfort LM, Fosbøl EL, Køber L, Torp-Pedersen C, Svendsen JH and Olesen MS: Atrial fibrillation: Age at diagnosis, incident cardiovascular events, and mortality. Eur Heart J. 45:2119–2129. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Liu X, Zhang W, Luo J, Shi W, Zhang X, Li Z, Qin X, Liu B and Wei Y: TRIM21 deficiency protects against atrial inflammation and remodeling post myocardial infarction by attenuating oxidative stress. Redox Biol. 62:1026792023. View Article : Google Scholar : PubMed/NCBI | |
|
Bossuyt J, Borst JM, Verberckmoes M, Bailey LRJ, Bers DM and Hegyi B: Protein kinase D1 regulates cardiac hypertrophy, potassium channel remodeling, and arrhythmias in heart failure. J Am Heart Assoc. 11:e0275732022. View Article : Google Scholar : PubMed/NCBI | |
|
Piccini JP: Atrial fibrillation and heart failure: Too much talk and not enough action. JACC Clin Electrophysiol. 9:581–582. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Wang H, Chen Y, Zhao S, Wang X, Lu K and Xiao H: Effect of Sox9 on TGF-β1-mediated atrial fibrosis. Acta Biochim Biophys Sin (Shanghai). 53:1450–1458. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Wolke C, Antileo E and Lendeckel U: WNT signaling in atrial fibrillation. Exp Biol Med (Maywood). 246:1112–1120. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Huang M, Huiskes FG, de Groot NMS and Brundel BJJM: The role of immune cells driving electropathology and atrial fibrillation. Cells. 13:3112021. View Article : Google Scholar | |
|
Yokoyama T, Kuga T, Itoh Y, Otake S, Omata C, Saitoh M and Miyazawa K: Smad2Δexon3 and Smad3 have distinct properties in signal transmission leading to TGF-β-induced cell motility. J Biol Chem. 299:1028202023. View Article : Google Scholar | |
|
Miyazawa K, Itoh Y, Fu H and Miyazono K: Receptor-activated transcription factors and beyond: Multiple modes of Smad2/3-dependent transmission of TGF-β signaling. J Biol Chem. 300:1072562024. View Article : Google Scholar | |
|
Hu HH, Chen DQ, Wang YN, Feng YL, Cao G, Vaziri ND and Zhao YY: New insights into TGF-β/Smad signaling in tissue fibrosis. Chem Biol Interact. 292:76–83. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Gao S, Li X, Jiang Q, Liang Q, Zhang F, Li S, Zhang R, Luan J, Zhu J, Gu X, et al: PKM2 promotes pulmonary fibrosis by stabilizing TGF-β1 receptor I and enhancing TGF-β1 signaling. Sci Adv. 8:eabo09872022. View Article : Google Scholar | |
|
Stolfi C, Troncone E, Marafini I and Monteleone G: Role of TGF-beta and Smad7 in gut inflammation, fibrosis and cancer. Biomolecules. 11:172020. View Article : Google Scholar : PubMed/NCBI | |
|
Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Li X, Zhu F, Meng W, Zhang F, Hong J, Zhang G and Wang F: CYP2J2/EET reduces vulnerability to atrial fibrillation in chronic pressure overload mice. J Cell Mol Med. 24:862–874. 2020. View Article : Google Scholar | |
|
Wang D, Wang X, Yang T, Tian H, Su Y and Wang Q: Long non-coding RNA Dancr affects myocardial fibrosis in atrial fibrillation mice via the MicroRNA-146b-5p/Smad5 axis. Acta Cardiol Sin. 39:841–853. 2023.PubMed/NCBI | |
|
Tian L, Wang Y and Jang YY: Wnt signaling in biliary development, proliferation, and fibrosis. Exp Biol Med (Maywood). 247:360–367. 2022. View Article : Google Scholar | |
|
Somanader DVN, Zhao P, Widdop RE and Samuel CS: The involvement of the Wnt/β-catenin signaling cascade in fibrosis progression and its therapeutic targeting by relaxin. Biochem Pharmacol. 223:1161302024. View Article : Google Scholar | |
|
Roberts JD, Murphy NP, Hamilton RM, Lubbers ER, James CA, Kline CF, Gollob MH, Krahn AD, Sturm AC, Musa H, et al: Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy. J Clin Invest. 129:3171–3184. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Lorenzon A, Calore M, Poloni G, De Windt LJ, Braghetta P and Rampazzo A: Wnt/β-catenin pathway in arrhythmogenic cardiomyopathy. Oncotarget. 8:60640–60655. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Lv X, Li J, Hu Y, Wang S, Yang C, Li C and Zhong G: Overexpression of miR-27b-3p targeting Wnt3a regulates the signaling pathway of Wnt/β-catenin and attenuates atrial fibrosis in rats with atrial fibrillation. Oxid Med Cell Longev. 2019:57037642019. View Article : Google Scholar | |
|
Lai YJ, Tsai FC, Chang GJ, Chang SH, Huang CC, Chen WJ and Yeh YH: miR-181b targets semaphorin 3A to mediate TGF-β-induced endothelial-mesenchymal transition related to atrial fibrillation. J Clin Invest. 132:e1425482022. View Article : Google Scholar | |
|
Zhang Z, Li L, Hu Z, Zhou L, Zhang Z, Xiong Y and Yao Y: Causal effects between atrial fibrillation and heart failure: Evidence from a bidirectional Mendelian randomization study. BMC Med Genomics. 16:1872023. View Article : Google Scholar : PubMed/NCBI | |
|
Sagris M, Vardas EP, Theofilis P, Antonopoulos AS, Oikonomou E and Tousoulis D: Atrial fibrillation: Pathogenesis, predisposing factors, and genetics. Int J Mol Sci. 23:62021. View Article : Google Scholar | |
|
Husti Z, Varró A and Baczkó I: Arrhythmogenic remodeling in the failing heart. Cells. 10:32032021. View Article : Google Scholar : PubMed/NCBI | |
|
Sun Z, Zhou D, Xie X, Wang S, Wang Z, Zhao W, Xu H and Zheng L: Cross-talk between macrophages and atrial myocytes in atrial fibrillation. Basic Res Cardiol. 111:632016. View Article : Google Scholar : PubMed/NCBI | |
|
Huiskes FG, Creemers EE and Brundel BJJM: Dissecting the molecular mechanisms driving electropathology in atrial fibrillation: Deployment of RNA sequencing and transcriptomic analyses. Cells. 12:22422023. View Article : Google Scholar : PubMed/NCBI | |
|
Maury P, Sanchis K, Djouadi K, Cariou E, Delasnerie H, Boveda S, Fournier P, Itier R, Mondoly P, Voglimacci-Stephan opoli Q, et al: Catheter ablation of atrial arrhythmias in cardiac amyloidosis: Impact on heart failure and mortality. PLoS One. 19:e03017532024. View Article : Google Scholar : PubMed/NCBI | |
|
Lei M, Wu L, Terrar DA and Huang CL: Modernized classification of cardiac antiarrhythmic drugs. Circulation. 138:1879–1896. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Mankad P and Kalahasty G: Antiarrhythmic drugs: Risks and benefits. Med Clin North Am. 103:821–834. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Romero G, Martin B, Gabris B and Salama G: Relaxin suppresses atrial fibrillation, reverses fibrosis and reduces inflammation in aged hearts. Biochem Pharmacol. 227:1164072024. View Article : Google Scholar : PubMed/NCBI | |
|
Martin B, Gabris B, Barakat AF, Henry BL, Giannini M, Reddy RP, Wang X, Romero G and Salama G: Relaxin reverses maladaptive remodeling of the aged heart through Wnt-signaling. Sci Rep. 9:185452019. View Article : Google Scholar : PubMed/NCBI | |
|
Hao H, Yan S, Zhao X, Han X, Fang N, Zhang Y, Dai C, Li W, Yu H, Gao Y, et al: Atrial myocyte-derived exosomal microRNA contributes to atrial fibrosis in atrial fibrillation. J Transl Med. 20:4072022. View Article : Google Scholar : PubMed/NCBI | |
|
Benali K, Khairy P, Hammache N, Petzl A, Da Costa A, Verma A, Andrade JG and Macle L: Procedure-related complications of catheter ablation for atrial fibrillation. J Am Coll Cardiol. 81:2089–2099. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Z, Xiao Y, Dai Y, Lin Q and Liu Q: Device therapy for patients with atrial fibrillation and heart failure with preserved ejection fraction. Heart Fail Rev. 29:417–430. 2024. View Article : Google Scholar : | |
|
Li S, Wang Y, Yang W, Zhou D, Zhuang B, Xu J, He J, Yin G, Fan X, Wu W, et al: Cardiac MRI risk stratification for dilated cardiomyopathy with left ventricular ejection fraction of 35% or higher. Radiology. 306:e2130592023. View Article : Google Scholar | |
|
Schultheiss HP, Fairweather D, Caforio ALP, Escher F, Hershberger RE, Lipshultz SE, Liu PP, Matsumori A, Mazzanti A, McMurray J and Priori SG: Dilated cardiomyopathy. Nat Rev Dis Primers. 5:322019. View Article : Google Scholar : PubMed/NCBI | |
|
Orphanou N, Papatheodorou E and Anastasakis A: Dilated cardiomyopathy in the era of precision medicine: Latest concepts and developments. Heart Fail Rev. 27:1173–1191. 2022. View Article : Google Scholar | |
|
Liu M, Zhai L, Yang Z, Li S, Liu T, Chen A, Wang L, Li Y, Li R, Li C, et al: Integrative proteomic analysis reveals the cytoskeleton regulation and mitophagy difference between ischemic cardiomyopathy and dilated cardiomyopathy. Mol Cell Proteomics. 22:1006672023. View Article : Google Scholar : PubMed/NCBI | |
|
Wang E, Zhou R, Li T, Hua Y, Zhou K, Li Y, Luo S and An Q: The molecular role of immune cells in dilated cardiomyopathy. Medicina (Kaunas). 59:12462023. View Article : Google Scholar : PubMed/NCBI | |
|
Yuan S, Zhang X, Zhan J, Xie R, Fan J, Dai B, Zhao Y, Yin Z, Liu Q, Wang DW, et al: Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy. Sci China Life Sci. 67:1155–1169. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Mado K, Chekulayev V, Shevchuk I, Puurand M, Tepp K and Kaambre T: On the role of tubulin, plectin, desmin, and vimentin in the regulation of mitochondrial energy fluxes in muscle cells. Am J Physiol Cell Physiol. 316:C657–C667. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang J, Cheng L, Li Z, Li H, Liu Y, Zhan H, Xu H, Huang Y, Feng F and Li Y: Immune cells and related cytokines in dilated cardiomyopathy. Biomed Pharmacother. 171:1161592024. View Article : Google Scholar : PubMed/NCBI | |
|
Cavusoglu Y, Tahmazov S, Murat S and Akay OM: Immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy: A potential therapeutic option. Rev Assoc Med Bras (1992). 69:90–96. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Zhong G, Chen C, Wu S, Chen J, Han Y, Zhu Q, Xu M, Nie Q and Wang L: Mechanism of angiotensin-converting enzyme inhibitors in the treatment of dilated cardiomyopathy based on a protein interaction network and molecular docking. Cardiovasc Diagn Ther. 13:534–549. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Tong X, Shen L, Zhou X, Wang Y, Chang S and Lu S: Comparative efficacy of different drugs for the treatment of dilated cardiomyopathy: A systematic review and network meta-analysis. Drugs R D. 23:197–210. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Jiao M, Wang X, Liang Y, Yang Y, Gu Y, Wang Z, Lv Z and Jin M: Effect of β-blocker therapy on the level of soluble ST2 protein in pediatric dilated cardiomyopathy. Medicina (Kaunas). 58:13392022. View Article : Google Scholar | |
|
Ferreira JP, Butler J, Zannad F, Filippatos G, Schueler E, Steubl D, Zeller C, Januzzi JL, Pocock S, Packer M and Anker SD: Mineralocorticoid receptor antagonists and empagliflozin in patients with heart failure and preserved ejection fraction. J Am Coll Cardiol. 79:1129–1137. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Eldemire R, Mestroni L and Taylor MRG: Genetics of dilated cardiomyopathy. Annu Rev Med. 75:417–426. 2024. View Article : Google Scholar : | |
|
Jordan E, Peterson L, Ai T, Asatryan B, Bronicki L, Brown E, Celeghin R, Edwards M, Fan J, Ingles J, et al: Evidence-based assessment of genes in dilated cardiomyopathy. Circulation. 144:7–19. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Koga-Ikuta A, Fukushima S, Ishibashi-Ueda H, Tadokoro N, Kakuta T, Watanabe T, Fukushima N, Suzuki K, Fukui T and Fujita T: Immunocompetent cells in durable ventricular assist device-implanted non-ischaemic dilated cardiomyopathy. Gen Thorac Cardiovasc Surg. 70:685–693. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Dziekiewicz M, Banaszewski M, Kuć M and Stępińska J: Intra-aortic balloon pump catheter insertion using a novel left external iliac artery approach in a case of chronic heart failure due to dilated cardiomyopathy. Am J Case Rep. 20:1826–1829. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang X, Wei R, Wang X, Zhang W, Li M, Ni T, Weng W and Li Q: The neutrophil-to-lymphocyte ratio is associated with all-cause and cardiovascular mortality among individuals with hypertension. Cardiovasc Diabetol. 23:1172024. View Article : Google Scholar : PubMed/NCBI | |
|
Messerli FH, Rimoldi SF and Bangalore S: The transition from hypertension to heart failure: Contemporary update. JACC Heart Fail. 5:543–551. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ma J, Li Y, Yang X, Liu K, Zhang X, Zuo X, Ye R, Wang Z, Shi R, Meng Q and Chen X: Signaling pathways in vascular function and hypertension: Molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 8:1682023. View Article : Google Scholar : PubMed/NCBI | |
|
Konukoglu D and Uzun H: Endothelial dysfunction and hypertension. Hypertension: From basic research to clinical practice. 511–540. 2017. | |
|
Watson T, Goon PKY and Lip GYH: Endothelial progenitor cells, endothelial dysfunction, inflammation, and oxidative stress in hypertension. Antioxid Redox Signal. 10:1079–1088. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu N, Guo ZF, Kazama K, Yi B, Tongmuang N, Yao H, Yang R, Zhang C, Qin Y, Han L and Sun J: Epigenetic regulation of vascular smooth muscle cell phenotypic switch and neointimal formation by PRMT5. Cardiovasc Res. 119:2244–2255. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Liard JF and Peters G: Role of the retention of water and sodium in two types of experimental renovascular hypertension in the rat. Pflugers Arch. 344:93–108. 1973. View Article : Google Scholar : PubMed/NCBI | |
|
Hu Y, Lin L, Zhang L, Li Y, Cui X, Lu M, Zhang Z, Guan X, Zhang M, Hao J, et al: Identification of circulating plasma proteins as a mediator of hypertension-driven cardiac remodeling: A mediation mendelian randomization study. Hypertension. 81:1132–1144. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang M, Han X, Yu T, Wang M, Luo W, Zou C, Li X, Li G, Wu G, Wang Y and Liang G: OTUD1 promotes pathological cardiac remodeling and heart failure by targeting STAT3 in cardiomyocytes. Theranostics. 13:2263–2280. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Holopainen T, Räsänen M, Anisimov A, Tuomainen T, Zheng W, Tvorogov D, Hulmi JJ, Andersson LC, Cenni B, Tavi P, et al: Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling. Proc Natl Acad Sci USA. 112:13063–13068. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Li L, Fu W, Gong X, Chen Z, Tang L, Yang D, Liao Q, Xia X, Wu H, Liu C, et al: The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction. Eur Heart J. 42:1415–1430. 2021. View Article : Google Scholar : | |
|
Bazgir F, Nau J, Nakhaei-Rad S, Amin E, Wolf MJ, Saucerman JJ, Lorenz K and Ahmadian MR: The microenvironment of the pathogenesis of cardiac hypertrophy. Cells. 12:17802023. View Article : Google Scholar : PubMed/NCBI | |
|
Nakamura M and Sadoshima J: Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol. 15:387–407. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Bertaud A, Joshkon A, Heim X, Bachelier R, Bardin N, Leroyer AS and Blot-Chabaud M: Signaling pathways and potential therapeutic strategies in cardiac fibrosis. Int J Mol Sci. 24:17562023. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang W, Wang Q, Feng Y, Chen X, Yang L, Xu M, Wang X, Li W, Niu X and Gao D: MicroRNA-26a protects the heart against hypertension-induced myocardial fibrosis. J Am Heart Assoc. 9:e0179702020. View Article : Google Scholar : PubMed/NCBI | |
|
Failer T, Amponsah-Offeh M, Neuwirth A, Kourtzelis I, Subramanian P, Mirtschink P, Peitzsch M, Matschke K, Tugtekin SM, Kajikawa T, et al: Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation. J Clin Invest. 132:e1261552022. View Article : Google Scholar : PubMed/NCBI | |
|
Rai R, Sun T, Ramirez V, Lux E, Eren M, Vaughan DE and Ghosh AK: Acetyltransferase p300 inhibitor reverses hypertension-induced cardiac fibrosis. J Cell Mol Med. 23:3026–3031. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Lv SL, Zeng ZF, Gan WQ, Wang WQ, Li TG, Hou YF, Yan Z, Zhang RX and Yang M: Lp-PLA2 inhibition prevents Ang II-induced cardiac inflammation and fibrosis by blocking macrophage NLRP3 inflammasome activation. Acta Pharmacol Sin. 42:2016–2032. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Johnson MT, Gudlur A, Zhang X, Xin P, Emrich SM, Yoast RE, Courjaret R, Nwokonko RM, Li W, Hempel N, et al: L-type Ca2+ channel blockers promote vascular remodeling through activation of STIM proteins. Proc Natl Acad Sci USA. 117:17369–17380. 2020. View Article : Google Scholar | |
|
Zhang Y, Murugesan P, Huang K and Cai H: NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets. Nat Rev Cardiol. 17:170–194. 2020. View Article : Google Scholar | |
|
Nardoianni G, Pala B, Scoccia A, Volpe M, Barbato E and Tocci G: Systematic review article: New drug strategies for treating resistant hypertension-the importance of a mechanistic, personalized approach. High Blood Press Cardiovasc Prev. 31:99–112. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang ZY, Yu YL, Asayama K, Hansen TW, Maestre GE and Staessen JA: Starting antihypertensive drug treatment with combination therapy: Controversies in hypertension-con side of the argument. Hypertension. 77:788–798. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Maron BJ, Desai MY, Nishimura RA, Spirito P, Rakowski H, Towbin JA, Dearani JA, Rowin EJ, Maron MS and Sherrid MV: Management of hypertrophic cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 79:390–414. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Maron BA, Wang RS, Carnethon MR, Rowin EJ, Loscalzo J, Maron BJ and Maron MS: What causes hypertrophic cardiomyopathy? Am J Cardiol. 179:74–82. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Cirino AL, Channaoui N and Ho C: Nonsyndromic hypertrophic cardiomyopathy overview. GeneReviews® [Internet]. Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and Amemiya A: University of Washington; Seattle, WA: 1993 | |
|
Bazan SGZ, Oliveira GO, Silveira CFDSMPD, Reis FM, Malagutte KNDS, Tinasi LSN, Bazan R, Hueb JC and Okoshi K: Hypertrophic cardiomyopathy: A review. Arq Bras Cardiol. 115:927–935. 2020.In English, Portuguese. View Article : Google Scholar : PubMed/NCBI | |
|
Homburger JR, Green EM, Caleshu C, Sunitha MS, Taylor RE, Ruppel KM, Metpally RP, Colan SD, Michels M, Day SM, et al: Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation. Proc Natl Acad Sci USA. 113:6701–6706. 2016. View Article : Google Scholar | |
|
Lin LR, Hu XQ, Lu LH, Dai JZ, Lin NN, Wang RH, Xie ZX and Chen XM: MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations. BMC Cardiovasc Disord. 22:2782022. View Article : Google Scholar : PubMed/NCBI | |
|
Parbhudayal RY, Harms HJ, Michels M, van Rossum AC, Germans T and van der Velden J: Increased myocardial oxygen consumption precedes contractile dysfunction in hypertrophic cardiomyopathy caused by pathogenic TNNT2 gene variants. J Am Heart Assoc. 9:e0153162020. View Article : Google Scholar : PubMed/NCBI | |
|
Fahed AC, Nemer G, Bitar FF, Arnaout S, Abchee AB, Batrawi M, Khalil A, Abou Hassan OK, DePalma SR, McDonough B, et al: Founder mutation in N terminus of cardiac troponin i causes malignant hypertrophic cardiomyopathy. Circ Genom Precis Med. 13:444–452. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Schulz EM, Wilder T, Chowdhury SA, Sheikh HN, Wolska BM, Solaro RJ and Wieczorek DF: Decreasing tropomyosin phosphorylation rescues tropomyosin-induced familial hypertrophic cardiomyopathy. J Biol Chem. 288:28925–28935. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Wijnker PJM and van der Velden J: Mutation-specific pathology and treatment of hypertrophic cardiomyopathy in patients, mouse models and human engineered heart tissue. Biochim Biophys Acta Mol Basis Dis. 1866:1657742020. View Article : Google Scholar : PubMed/NCBI | |
|
Enriquez AD and Goldman ME: Management of hypertrophic cardiomyopathy. Ann Glob Health. 80:35–45. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Lehman SJ, Crocini C and Leinwand LA: Targeting the sarcomere in inherited cardiomyopathies. Nat Rev Cardiol. 19:353–363. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Pradeep R, Akram A, Proute MC, Kothur NR, Georgiou P, Serhiyenia T, Shi W, Kerolos ME and Mostafa JA: Understanding the genetic and molecular basis of familial hypertrophic cardiomyopathy and the current trends in gene therapy for its management. Cureus. 13:e175482021.PubMed/NCBI | |
|
Liu T, Hao Y, Zhang Z, Zhou H, Peng S, Zhang D, Li K, Chen Y and Chen M: Advanced cardiac patches for the treatment of myocardial infarction. Circulation. 149:2002–2020. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Golforoush P, Yellon DM and Davidson SM: Mouse models of atherosclerosis and their suitability for the study of myocardial infarction. Basic Res Cardiol. 115:732020. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang H, Fang T and Cheng Z: Mechanism of heart failure after myocardial infarction. J Int Med Res. 51:30006052312025732023. View Article : Google Scholar : PubMed/NCBI | |
|
Jenča D, Melenovský V, Stehlik J, Staněk V, Kettner J, Kautzner J, Adámková V and Wohlfahrt P: Heart failure after myocardial infarction: Incidence and predictors. ESC Heart Fail. 8:222–237. 2021. View Article : Google Scholar | |
|
Feng R, Wang D, Li T, Liu X, Peng T, Liu M, Ren G, Xu H, Luo H, Lu D, et al: Elevated SLC40A1 impairs cardiac function and exacerbates mitochondrial dysfunction, oxidative stress, and apoptosis in ischemic myocardia. Int J Biol Sci. 20:414–432. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Dharmakumar R, Nair AR, Kumar A and Francis J: Myocardial infarction and the fine balance of iron. JACC Basic Transl Sci. 6:581–583. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao WK, Zhou Y, Xu TT and Wu Q: Ferroptosis: Opportunities and challenges in myocardial ischemia-reperfusion injury. Oxid Med Cell Longev. 2021:99296872021. View Article : Google Scholar : PubMed/NCBI | |
|
Marunouchi T, Onda S, Kurasawa M and Tanonaka K: Angiotensin II is involved in MLKL activation during the development of heart failure following myocardial infarction in rats. Biol Pharm Bull. 47:809–817. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Santagostino SF, Assenmacher CA, Tarrant JC, Adedeji AO and Radaelli E: Mechanisms of regulated cell death: Current perspectives. Vet Pathol. 58:596–623. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Li A, Gao M, Liu B, Qin Y, Chen L, Liu H, Wu H and Gong G: Mitochondrial autophagy: Molecular mechanisms and implications for cardiovascular disease. Cell Death Dis. 13:4442022. View Article : Google Scholar : PubMed/NCBI | |
|
Held PH, Yusuf S and Furberg CD: Calcium channel blockers in acute myocardial infarction and unstable angina: An overview. BMJ. 299:1187–1192. 1989. View Article : Google Scholar : PubMed/NCBI | |
|
Makarewich CA, Zhang H, Davis J, Correll RN, Trappanese DM, Hoffman NE, Troupes CD, Berretta RM, Kubo H, Madesh M, et al: Transient receptor potential channels contribute to pathological structural and functional remodeling after myocardial infarction. Circ Res. 115:567–580. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Cui T, Liu W, Yu C, Ren J, Li Y, Shi X, Li Q and Zhang J: Protective effects of allicin on acute myocardial infarction in rats via hydrogen sulfide-mediated regulation of coronary arterial vasomotor function and myocardial calcium transport. Front Pharmacol. 12:7522442022. View Article : Google Scholar : PubMed/NCBI | |
|
Pietrzykowski Ł, Michalski P, Kosobucka A, Kasprzak M, Fabiszak T, Stolarek W, Siller-Matula JM and Kubica A: Medication adherence and its determinants in patients after myocardial infarction. Sci Rep. 10:120282020. View Article : Google Scholar : PubMed/NCBI | |
|
Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R and Dagenais G: Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 342:145–153. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Khan SU, Singh M, Valavoor S, Khan MU, Lone AN, Khan MZ, Khan MS, Mani P, Kapadia SR, Michos ED, et al: Dual antiplatelet therapy after percutaneous coronary intervention and drug-eluting stents: A systematic review and network meta-analysis. Circulation. 142:1425–1436. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Yandrapalli S, Andries G, Gupta S, Dajani AR and Aronow WS: Investigational drugs for the treatment of acute myocardial infarction: Focus on antiplatelet and anticoagulant agents. Expert Opin Investig Drugs. 28:223–234. 2019. View Article : Google Scholar | |
|
AIM-HIGH Investigators; Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K and Weintraub W: Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 365:2255–2267. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Tsai IT and Sun CK: Stem cell therapy against ischemic heart disease. Int J Mol Sci. 25:37782024. View Article : Google Scholar : PubMed/NCBI | |
|
Broch K, Anstensrud AK, Woxholt S, Sharma K, Tøllefsen IM, Bendz B, Aakhus S, Ueland T, Amundsen BH, Damås JK, et al: Randomized trial of interleukin-6 receptor inhibition in patients with acute ST-segment elevation myocardial infarction. J Am Coll Cardiol. 77:1845–1855. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Shi S, Chen Y, Luo Z, Nie G and Dai Y: Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy. Cell Commun Signal. 21:612023. View Article : Google Scholar : PubMed/NCBI | |
|
Ye X, Li Y, Lv B, Qiu B, Zhang S, Peng H, Kong W, Tang C, Huang Y, Du J and Jin H: Endogenous hydrogen sulfide persulfidates caspase-3 at cysteine 163 to inhibit doxorubicin-induced cardiomyocyte apoptosis. Oxid Med Cell Longev. 2022:61537722022. View Article : Google Scholar : PubMed/NCBI | |
|
Gammella E, Recalcati S, Rybinska I, Buratti P and Cairo G: Iron-induced damage in cardiomyopathy: Oxidative-dependent and independent mechanisms. Oxid Med Cell Longev. 2015:2301822015. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng CF and Lian WS: Prooxidant mechanisms in iron overload cardiomyopathy. Biomed Res Int. 2013:7405732013. View Article : Google Scholar : PubMed/NCBI | |
|
Fatmi A, Saadi W, Beltrán-García J, García-Giménez JL and Pallardó FV: The endothelial glycocalyx and neonatal sepsis. Int J Mol Sci. 24:3642022. View Article : Google Scholar | |
|
Carthy CM, Yang D, Anderson DR, Wilson JE and McManus BM: Myocarditis as systemic disease: New perspectives on pathogenesis. Clin Exp Pharmacol Physiol. 24:997–1003. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Lasrado N and Reddy J: An overview of the immune mechanisms of viral myocarditis. Rev Med Virol. 30:1–14. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Dimitropoulos G, Tahrani AA and Stevens MJ: Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes. 5:17–39. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Lin S, Dai S, Lin J, Liang X, Wang W, Huang W, Ye B and Hong X: Oridonin relieves angiotensin II-induced cardiac remodeling via inhibiting GSDMD-mediated inflammation. Cardiovasc Ther. 2022:31679592022. View Article : Google Scholar : PubMed/NCBI | |
|
Chen S, Huang Z, Liang Y, Zhao X, Aobuliksimu X, Wang B, He Y, Kang Y, Huang H, Li Q, et al: Five-year mortality of heart failure with preserved, mildly reduced, and reduced ejection fraction in a 4880 Chinese cohort. ESC Heart Fail. 9:2336–2347. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Liu M, López de Juan Abad B and Cheng K: Cardiac fibrosis: Myofibroblast-mediated pathological regulation and drug delivery strategies. Adv Drug Deliv Rev. 173:504–519. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Ravassa S, López B, Treibel TA, San José G, Losada-Fuentenebro B, Tapia L, Bayés-Genís A, Díez J and González A: Cardiac Fibrosis in heart failure: Focus on non-invasive diagnosis and emerging therapeutic strategies. Mol Aspects Med. 93:1011942023. View Article : Google Scholar : PubMed/NCBI | |
|
Martin TG, Juarros MA and Leinwand LA: Regression of cardiac hypertrophy in health and disease: Mechanisms and therapeutic potential. Nat Rev Cardiol. 20:347–363. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Su Z, Yang Z, Xu Y, Chen Y and Yu Q: Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer. 14:482015. View Article : Google Scholar : PubMed/NCBI | |
|
Dong Y, Liu C, Zhao Y, Ponnusamy M, Li P and Wang K: Role of noncoding RNAs in regulation of cardiac cell death and cardiovascular diseases. Cell Mol Life Sci. 75:291–300. 2018. View Article : Google Scholar | |
|
Cai K, Jiang H, Zou Y, Song C, Cao K, Chen S, Wu Y, Zhang Z, Geng D, Zhang N, et al: Programmed death of cardiomyocytes in cardiovascular disease and new therapeutic approaches. Pharmacol Res. 206:1072812024. View Article : Google Scholar : PubMed/NCBI | |
|
Chiong M, Wang ZV, Pedrozo Z, Cao DJ, Troncoso R, Ibacache M, Criollo A, Nemchenko A, Hill JA and Lavandero S: Cardiomyocyte death: Mechanisms and translational implications. Cell Death Dis. 2:e2442011. View Article : Google Scholar : PubMed/NCBI | |
|
Topriceanu CC, Pereira AC, Moon JC, Captur G and Ho CY: Meta-analysis of penetrance and systematic review on transition to disease in genetic hypertrophic cardiomyopathy. Circulation. 149:107–123. 2024. View Article : Google Scholar : | |
|
Ye C, Zheng F, Wu N, Zhu GQ and Li XZ: Extracellular vesicles in vascular remodeling. Acta Pharmacol Sin. 43:2191–2201. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Jordan-Rios A, Cannatà A, Bromage D and McDonagh T: Challenges in the implementation of medical therapy in heart failure. JACC Heart Fail. 11:607–609. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Pacesa M, Pelea O and Jinek M: Past, present, and future of CRISPR genome editing technologies. Cell. 187:1076–1100. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Xiao Y, Zhao J, Tuazon JP, Borlongan CV and Yu G: MicroRNA-133a and myocardial infarction. Cell Transplant. 28:831–838. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Reichart D, Newby GA, Wakimoto H, Lun M, Gorham JM, Curran JJ, Raguram A, DeLaughter DM, Conner DA, Marsiglia JDC, et al: Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice. Nat Med. 29:412–421. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Morris KV and Mattick JS: The rise of regulatory RNA. Nat Rev Genet. 15:423–437. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Shim JS, Song WJ and Morice AH: Drug-induced cough. Physiol Res. 69(Suppl 1): S81–S92. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Wong GW and Wright JM: Blood pressure lowering efficacy of nonselective beta-blockers for primary hypertension. Cochrane Database Syst Rev. 2014:CD0074522024. | |
|
Cheng CJ, Rodan AR and Huang CL: Emerging targets of diuretic therapy. Clin Pharmacol Ther. 102:420–435. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Haley KE, Almas T, Shoar S, Shaikh S, Azhar M, Cheema FH and Hameed A: The role of anti-inflammatory drugs and nanoparticle-based drug delivery models in the management of ischemia-induced heart failure. Biomed Pharmacother. 142:1120142021. View Article : Google Scholar : PubMed/NCBI | |
|
Pala R, Anju VT, Dyavaiah M, Busi S and Nauli SM: Nanoparticle-mediated drug delivery for the treatment of cardiovascular diseases. Int J Nanomedicine. 15:3741–3769. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Qiu R, Han S, Wei X, Zhong C, Li M, Hu J, Wang P, Zhao C, Chen J and Shang H: Development of a core outcome set for the benefits and adverse events of acute heart failure in clinical trials of traditional Chinese medicine and western medicine: A study protocol. Front Med (Lausanne). 8:6770682021. View Article : Google Scholar : PubMed/NCBI | |
|
Chen X, Ma Y, Li J, Yao L, Gui M, Lu B, Zhou X, Wang M and Fu D: The efficacy of ginseng-containing traditional Chinese medicine in patients with acute decompensated heart failure: A systematic review and meta-analysis. Front Pharmacol. 13:10830012023. View Article : Google Scholar : PubMed/NCBI | |
|
Ji MY, Bo A, Yang M, Xu JF, Jiang LL, Zhou BC and Li MH: The pharmacological effects and health benefits of platycodon grandiflorus-a medicine food homology species. Foods. 9:1422020. View Article : Google Scholar : PubMed/NCBI | |
|
Tang MM, Zhao ST, Li RQ and Hou W: Therapeutic mechanisms of ginseng in coronary heart disease. Front Pharmacol. 14:12710292023. View Article : Google Scholar : PubMed/NCBI | |
|
Yang L, Jiang H, Wang S, Hou A, Man W, Zhang J, Guo X, Yang B, Kuang H and Wang Q: Discovering the major antitussive, expectorant, and anti-inflammatory bioactive constituents in Tussilago farfara L. based on the spectrum-effect relationship combined with chemometrics. Molecules. 25:6202020. View Article : Google Scholar : PubMed/NCBI | |
|
Tan D, Tseng HHL, Zhong Z, Wang S, Vong CT and Wang Y: Glycyrrhizic acid and its derivatives: Promising candidates for the management of type 2 diabetes mellitus and its complications. Int J Mol Sci. 23:109882022. View Article : Google Scholar : PubMed/NCBI | |
|
Feng Q, Ling L, Yuan H, Guo Z and Ma J: Ginsenoside Rd: A promising target for ischemia-reperfusion injury therapy (A mini review). Biomed Pharmacother. 171:1161112024. View Article : Google Scholar : PubMed/NCBI | |
|
MacRitchie N and Maffia P: Light sheet fluorescence microscopy for quantitative three-dimensional imaging of vascular remodelling. Cardiovasc Res. 117:348–350. 2021. View Article : Google Scholar : | |
|
Yu B, Lu Q, Li J, Cheng X, Hu H, Li Y, Che T, Hua Y, Jiang H, Zhang Y, et al: Cryo-EM structure of human HCN3 channel and its regulation by cAMP. J Biol Chem. 300:1072882024. View Article : Google Scholar : PubMed/NCBI | |
|
Li H, Zhang X, Wang F, Zhou L, Yin Z, Fan J, Nie X, Wang P, Fu XD, Chen C and Wang DW: MicroRNA-21 lowers blood pressure in spontaneous hypertensive rats by upregulating mitochondrial translation. Circulation. 134:734–751. 2016. View Article : Google Scholar : PubMed/NCBI |
