Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
October-2025 Volume 56 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October-2025 Volume 56 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review)

  • Authors:
    • Xiaotong Ma
    • Ran Wei
    • Anni Song
    • Xinyi Zhang
    • Jianpeng Zou
    • Shijie Hao
  • View Affiliations / Copyright

    Affiliations: College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China, Department of Rehabilitation and Physiotherapy, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, Shandong 250011, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 158
    |
    Published online on: July 29, 2025
       https://doi.org/10.3892/ijmm.2025.5599
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Cardiovascular disease (CVD) is a major global health threat, as its incidence and mortality rates continue to rise, highlighting the urgent need for effective therapeutic strategies. Histone deacetylase 4 (HDAC4), a member of class IIa HDACs, has attracted increasing attention in recent years for its role in CVD. Studies have shown that HDAC4 can influence the development and progression of CVD such as cardiac hypertrophy, hypertension and atherosclerosis by regulating key pathophysiological processes including inflammation, fibrosis and apoptosis. The present review focuses on the functional roles of HDAC4 in CVD and examines the effects of pharmacological agents and physical exercise on its expression. Future research should further elucidate the molecular mechanisms underlying HDAC4's involvement in CVD to provide new theoretical foundations for clinical diagnosis and treatment.
View Figures

Figure 1

Schematic diagram of human histone
deacetylase 4 functional domains. KDAC, Lysine deacetylase; NLS,
Nuclear localization sequence; NES, Nuclear export sequence; aa,
amino acid.

Figure 2

Function of HDAC4 in CVD. (A)
Regulating the inflammatory response. (B) Regulation of myocardial
fibrosis. (C) Regulation of apoptosis. AngII, angiotensinII; HDAC4,
histone deacetylase 4; HuR, human antigen R; lncRNA CASC11, long
non-coding RNA cancer susceptibility candidate 11; p-NF-κB,
phosphorylated nuclear factor-kappa B; VCAM-1, vascular cell
adhesion molecule-1; IL-10, interleukin-10; TNF-α, tumor necrosis
factor-α; α-SMA, α-smooth muscle actin; ABHD5, abhydrolase domain
containing 5; Nppb, natriuretic peptide B; Nr4a1, nuclear receptor
subfamily 4 group A member 1; Gftpt2,
glutamine-fructose-6-phosphate transaminase 2; Pdk4, pyruvate
dehydrogenase kinase 4; Col3a1, collagen type III alpha 1 chain;
lncRNA TUG1, long non-coding RNA taurine-upregulated gene 1; Bcl-2,
B-cell lymphoma 2; Bax, Bcl-2-associated X protein.

Figure 3

Role of HDAC4 in cardiac hypertrophy.
Most studies have shown that AngII induces cardiac hypertrophy, and
HDAC4 can promote the expression of ANP, BNP, β-MHC and ANF,
thereby contributing to myocardial hypertrophy. It is well
established that the CaMKII/HDAC4/MEF2C axis, as a classical
signaling pathway, plays a crucial role in exacerbating cardiac
hypertrophy. Additionally, HDAC4 mediates the effects of WWP1,
CKIP-1, lncRNA MHRT and FGF23 in the progression of myocardial
hypertrophy. HDAC4, histone deacetylase 4; AngII, angiotensinII;
PP2A, phosphatase-2A; CKIP-1, casein kinase-2 interacting
protein-1; WWP1, WW domain-containing E3 ubiquitin protein ligase
1; DVL2, disheveled segment polarity protein 2; CaMKII,
calcium/calmodulin-dependent protein kinase II; MEF2C, myocyte
enhancer factor 2C; ANP, atrial natriuretic peptide; BNP, brain
natriuretic peptide; β-MHC, β-myosin heavy chain; ANF, atrial
natriuretic factor; MHRT, myosin heavy chain associated RNA
transcript; SP1, specificity protein 1; SIRT1, sirtuin1; PGC1-α,
proliferator-activated receptor γ coactivator 1α; PPARα, peroxisome
proliferator-activated receptor α; ERβ, estrogen receptor β; GLP-1,
glucagon-like peptide-1; Nox4, NADPH oxidase 4; FGF23, fibroblast
growth factor 23; IP3, inositol 1,4,5-triphosphate; Gal-1,
galectin-1; LTCC, L-type calcium channel; Nppa, natriuretic peptide
A; Myh7, myosin heavy chain 7.

Figure 4

Role of HDAC4 in coronary heart
disease, sick sinus syndrome and myocardial ischemia-reperfusion
injury. HDAC4 can improve CHD by suppressing myocardial
inflammatory responses. By contrast, HDAC4 may exacerbate disease
progression in SSS and myocardial ischemia-reperfusion injury by
aggravating oxidative stress, apoptosis, and lactate dehydrogenase
leakage. HDAC4, histone deacetylase 4; Scr, serum creatinine;
LDL-C, low-density lipoprotein cholesterol; CRP, C-reactive
protein; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β;
H2O2, hydrogen peroxide; HuR, human antigen
R; lncRNA CASC11, long non-coding RNA cancer susceptibility
candidate 11; Trx2, thioredoxin-2; ROS, reactive oxygen species;
MEF2C, myocyte enhancer factor 2C; HCN4,
hyperpolarization-activated cyclic nucleotide-gated potassium
channel 4; SOD1, superoxide dismutase 1; GLUT1, glucose transporter
type 1; lncRNA TUG1, long non-coding RNA taurine-upregulated gene
1; LC3-I/II, microtubule-associated protein 1A/1B-light chain 3;
LDH, lactate dehydrogenase.

Figure 5

Role of HDAC4 in hyperthyroid heart
disease, myocardial infarction and heart failure. HDAC4 exacerbates
T3- or T4-induced HHD progression by inducing ANP, BNP, α-actin and
α-MHC. Similarly, HDAC4 can also promote MI by upregulating ANP and
suppressing myocardial autophagy. Additionally, studies have shown
that HDAC4 nucleocytoplasmic shuttling plays a significant role in
HF. HDAC4, histone deacetylase 4; T4, L-thyroxine; CaMKII,
calcium/calmodulin-dependent protein kinase II; MEF2a, myocyte
enhancer factor 2a; ANP, atrial natriuretic peptide; BNP, brain
natriuretic peptide; α-MHC,α-myosin heavy chain; GRK4, G
protein-coupled receptor kinase 4; Yy1, Yin-yang1; ANP, atrial
natriuretic peptide; LC3-II, microtubule-associated protein
1A/1B-light chain 3; IκBα, inhibitor of nuclear factor κB α; NF-κB,
nuclear factor kappa B; SP1, specificity protein 1; PPARα,
peroxisome proliferator-activated receptor α.

Figure 6

Role of HDAC4 in hypertension and
atherosclerosis. HDAC4 promotes hypertension by enhancing the
expression of inflammatory factors such as VCAM-1, IL-6 and
p-NF-κB. Additionally, HDAC4 can interact with GATA6 to upregulate
the expression of cell cycle-related genes (E2F3 and cyclin E),
thereby contributing to hypertension. By contrast, HDAC4 exerts
inhibitory effects in AS. On one hand, HDAC4 suppresses AS by
upregulating the expression of the anti-apoptotic protein Bcl2. On
the other hand, HDAC4 also alleviates AS by inhibiting vascular
calcification. AngII, Angiotensin II; HDAC4, histone deacetylase 4;
FoxO3a, forkhead box protein O3a; LC3-II, microtubule-associated
protein 1A/1B-light chain 3; IL-6, interleukin-6; VCAM-1, vascular
cell adhesion molecule-1; iNOS, inducible nitric oxide synthase;
SP1, specificity protein 1; NF-κB, nuclear factor kappa B; CaMKIIα,
calcium/calmodulin-dependent protein kinase IIα; GATA6,
GATA-binding factor 6; PKD1, pyruvate dehydrogenase kinase 1; ALP,
alkaline phosphatase; BMP-2, bone morphogenetic protein 2; KLF7,
Krüppel-like factor 7; NCOR1, nuclear receptor corepressor 1; GMR,
glucose metabolic reprogramming; Bcl2, B-cell lymphoma 2.

Figure 7

Potential mechanism of HDAC4 in
cardiovascular diseases. HDAC4, histone deacetylase 4; SAN,
sinoatrial node; ROS, reactive oxygen species.
View References

1 

Li P, Ge J and Li H: Lysine acetyltransferases and lysine deacetylases as targets for cardiovascular disease. Nat Rev Cardiol. 17:96–115. 2020. View Article : Google Scholar

2 

Haberland M, Montgomery RL and Olson EN: The many roles of histone deacetylases in development and physiology: Implications for disease and therapy. Nat Rev Genet. 10:32–42. 2009. View Article : Google Scholar

3 

Zhang D, Hu X, Henning RH and Brundel BJ: Keeping up the balance: Role of HDACs in cardiac proteostasis and therapeutic implications for atrial fibrillation. Cardiovasc Res. 109:519–526. 2016. View Article : Google Scholar

4 

Backs J and Olson EN: Control of cardiac growth by histone acetylation/deacetylation. Circ Res. 98:15–24. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Hohl M, Wagner M, Reil JC, Müller SA, Tauchnitz M, Zimmer AM, Lehmann LH, Thiel G, Böhm M, Backs J and Maack C: HDAC4 controls histone methylation in response to elevated cardiac load. J Clin Invest. 123:1359–1370. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Wang Z, Qin G and Zhao TC: HDAC4: Mechanism of regulation and biological functions. Epigenomics. 6:139–150. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Ouyang J, Wang H and Huang J: The role of lactate in cardiovascular diseases. Cell Commun Signal. 21:3172023. View Article : Google Scholar : PubMed/NCBI

8 

Alves PKN, Schauer A, Augstein A, Männel A, Barthel P, Joachim D, Friedrich J, Prieto ME, Moriscot AS, Linke A and Adams V: Leucine Supplementation improves diastolic function in HFpEF by HDAC4 inhibition. Cells. 12:25612023. View Article : Google Scholar : PubMed/NCBI

9 

Ling S, Sun Q, Li Y, Zhang L, Zhang P, Wang X, Tian C, Li Q, Song J, Liu H, et al: CKIP-1 inhibits cardiac hypertrophy by regulating class II histone deacetylase phosphorylation through recruiting PP2A. Circulation. 126:3028–3040. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Li J, Gao Q, Wang S, Kang Z, Li Z, Lei S, Sun X, Zhao M, Chen X, Jiao G, et al: Sustained increased CaMKII phosphorylation is involved in the impaired regression of isoproterenol-induced cardiac hypertrophy in rats. J Pharmacol Sci. 144:30–42. 2020. View Article : Google Scholar : PubMed/NCBI

11 

Ginnan R, Sun LY, Schwarz JJ and Singer HA: MEF2 is regulated by CaMKIIdelta2 and a HDAC4-HDAC5 heterodimer in vascular smooth muscle cells. Biochem J. 444:105–114. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Berthouze-Duquesnes M, Lucas A, Sauliere A, Sin YY, Laurent AC, Galés C, Baillie G and Lezoualc'h F: Specific interactions between Epac1, β-arrestin2 and PDE4D5 regulate β-adrenergic receptor subtype differential effects on cardiac hypertrophic signaling. Cell Signal. 25:970–980. 2013. View Article : Google Scholar

13 

Guo Z, Wu Y, Feng Q, Wang C, Wang Z, Zhu Y, Lu X, Chen W, Yang Q and Huo Y: Circulating HDAC4 reflects lipid profile, coronary stenosis and inflammation in coronary heart disease patients. Biomark Med. 17:41–49. 2023. View Article : Google Scholar : PubMed/NCBI

14 

Kong Q, Hao Y, Li X, Wang X, Ji B and Wu Y: HDAC4 in ischemic stroke: Mechanisms and therapeutic potential. Clin Epigenetics. 10:1172018. View Article : Google Scholar : PubMed/NCBI

15 

Chen Z, Zhang Z, Guo L, Wei X, Zhang Y, Wang X and Wei L: The role of histone deacetylase 4 during chondrocyte hypertrophy and endochondral bone development. Bone Joint Res. 9:82–89. 2020. View Article : Google Scholar : PubMed/NCBI

16 

Mathias RA, Guise AJ and Cristea IM: Post-translational modifications regulate class IIa histone deacetylase (HDAC) function in health and disease. Mol Cell Proteomics. 14:456–470. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Cuttini E, Goi C, Pellarin E, Vida R and Brancolini C: HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications. Front Mol Biosci. 10:11166602023. View Article : Google Scholar : PubMed/NCBI

18 

Duarte LRF, Pinho V, Rezende BM and Teixeira MM: Resolution of inflammation in acute graft-versus-host-disease: Advances and perspectives. Biomolecules. 12:752022. View Article : Google Scholar : PubMed/NCBI

19 

Liberale L, Badimon L, Montecucco F, Luscher TF, Libby P and Camici GG: Inflammation, aging, and cardiovascular disease: JACC review topic of the week. J Am Coll Cardiol. 79:837–847. 2022. View Article : Google Scholar : PubMed/NCBI

20 

Cui C, Liu L, Qi Y, Han N, Xu H, Wang Z, Shang X, Han T, Zha Y, Wei X and Wu Z: Joint association of TyG index and high sensitivity C-reactive protein with cardiovascular disease: A national cohort study. Cardiovasc Diabetol. 23:1562024. View Article : Google Scholar : PubMed/NCBI

21 

Fredman G and Serhan CN: Specialized pro-resolving mediators in vascular inflammation and atherosclerotic cardiovascular disease. Nat Rev Cardiol. 21:808–823. 2024. View Article : Google Scholar : PubMed/NCBI

22 

Yang D, Xiao C, Long F, Su Z, Jia W, Qin M, Huang M, Wu W, Suguro R, Liu X and Zhu Y: HDAC4 regulates vascular inflammation via activation of autophagy. Cardiovasc Res. 114:1016–1028. 2018. View Article : Google Scholar : PubMed/NCBI

23 

Usui T, Okada M, Hara Y and Yamawaki H: Exploring calmodulin-related proteins, which mediate development of hypertension, in vascular tissues of spontaneous hypertensive rats. Biochem Biophys Res Commun. 405:47–51. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Hu K, Huang MJ, Ling S, Li YX, Cao XY, Chen YF, Lei JM, Fu WZ and Tan BF: LncRNA CASC11 upregulation promotes HDAC4 to alleviate oxidized low-density lipoprotein-induced injury of cardiac microvascular endothelial cells. Kaohsiung J Med Sci. 39:758–768. 2023. View Article : Google Scholar : PubMed/NCBI

25 

Ravassa S, Lopez B, Treibel TA, José GS, 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

26 

Zhang Y, Gao F, Tang Y, Xiao J, Li C, Ouyang Y and Hou Y: Valproic acid regulates Ang II-induced pericyte-myofibroblast trans-differentiation via MAPK/ERK pathway. Am J Transl Res. 10:1976–1989. 2018.PubMed/NCBI

27 

Zhang LX, DeNicola M, Qin X, Du J, Ma J, Zhao YT, Zhuang S, Liu PY, Wei L, Qin G, et al: Specific inhibition of HDAC4 in cardiac progenitor cells enhances myocardial repairs. Am J Physiol Cell Physiol. 307:C358–C372. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Zhang LX, Du J, Zhao YT, Wang J, Zhang S, Dubielecka PM, Wei L, Zhuang S, Qin G, Chin YE and Zhao TC: Transgenic overexpression of active HDAC4 in the heart attenuates cardiac function and exacerbates remodeling in infarcted myocardium. J Appl Physiol (1985). 125:1968–1978. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Jebessa ZH, Shanmukha KD, Dewenter M, Lehmann LH, Xu C, Schreiter F, Siede D, Gong XM, Worst BC, Federico G, et al: The lipid droplet-associated protein ABHD5 protects the heart through proteolysis of HDAC4. Nat Metab. 1:1157–1167. 2019. View Article : Google Scholar : PubMed/NCBI

30 

Lehmann LH, Jebessa ZH, Kreusser MM, Horsch A, He T, Kronlage M, Dewenter M, Sramek V, Oehl U, Krebs-Haupenthal J, et al: A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway. Nat Med. 24:62–72. 2018. View Article : Google Scholar

31 

Zhan J, Wang J, Liang Y, Wang L, Huang L, Liu S, Zeng X, Zeng E and Wang H: Apoptosis dysfunction: Unravelling the interplay between ZBP1 activation and viral invasion in innate immune responses. Cell Commun Signal. 22:1492024. View Article : Google Scholar : PubMed/NCBI

32 

Emdad L, Bhoopathi P, Talukdar S, Pradhan AK, Sarkar D, Wang XY, Das SK and Fisher PB: Recent insights into apoptosis and toxic autophagy: The roles of MDA-7/IL-24, a multidimensional anti-cancer therapeutic. Semin Cancer Biol. 66:140–154. 2020. View Article : Google Scholar :

33 

Zou G, Zhong W, Wu F, Wang X and Liu L: Catalpol attenuates cardiomyocyte apoptosis in diabetic cardiomyopathy via Neat1/miR-140-5p/HDAC4 axis. Biochimie. 165:90–99. 2019. View Article : Google Scholar : PubMed/NCBI

34 

Zhang L, Wang H, Zhao Y, Wang J, Dubielecka PM, Zhuang S, Qin G, Chin YE, Kao RL and Zhao TC: Myocyte-specific overexpressing HDAC4 promotes myocardial ischemia/reperfusion injury. Mol Med. 24:372018. View Article : Google Scholar : PubMed/NCBI

35 

Wu X, Liu Y, Mo S, Wei W, Ye Z and Su Q: LncRNA TUG1 competitively binds to miR-340 to accelerate myocardial ischemia-reperfusion injury. FASEB J. 35:e211632021.

36 

Zhang F, Cheng N, Du J, Zhang H and Zhang C: MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis. BMC Cardiovasc Disord. 21:1722021. View Article : Google Scholar : PubMed/NCBI

37 

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

38 

Ago T, Liu T, Zhai P, Chen W, Li H, Molkentin JD, Vatner SF and Sadoshima J: A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy. Cell. 133:978–993. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Backs J, Song K, Bezprozvannaya S, Chang S and Olson EN: CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J Clin Invest. 116:1853–1864. 2006. View Article : Google Scholar : PubMed/NCBI

40 

Fujioka R, Yamamoto T, Maruta A, Nakamura Y, Tominaga N, Inamitsu M, Oda T, Kobayashi S and Yano M: Herpud1 modulates hypertrophic signals independently of calmodulin nuclear translocation in rat myocardium-derived H9C2 cells. Biochem Biophys Res Commun. 652:61–67. 2023. View Article : Google Scholar : PubMed/NCBI

41 

Zheng L, Wang J, Zhang R, Zhang Y, Geng J, Cao L, Zhao X, Geng J, Du X, Hu Y and Cong H: Angiotensin II mediates cardiomyocyte hypertrophy in atrial cardiomyopathy via epigenetic transcriptional regulation. Comput Math Methods Med. 2022:63121002022. View Article : Google Scholar : PubMed/NCBI

42 

Zhao D, Zhong G, Li J, Pan J, Zhao Y, Song H, Sun W, Jin X, Li Y, Du R, et al: Targeting E3 ubiquitin ligase WWP1 prevents cardiac hypertrophy through destabilizing DVL2 via inhibition of K27-linked ubiquitination. Circulation. 144:694–711. 2021. View Article : Google Scholar : PubMed/NCBI

43 

Li C, Cai X, Sun H, Bai T, Zheng X, Zhou XW, Chen X, Gill DL, Li J and Tang XD: The deltaA isoform of calmodulin kinase II mediates pathological cardiac hypertrophy by interfering with the HDAC4-MEF2 signaling pathway. Biochem Biophys Res Commun. 409:125–130. 2011. View Article : Google Scholar : PubMed/NCBI

44 

Lairez O, Cognet T, Schaak S, Calise D, Guilbeau-Frugier C, Parini A and Mialet-Perez J: Role of serotonin 5-HT2A receptors in the development of cardiac hypertrophy in response to aortic constriction in mice. J Neural Transm (Vienna). 120:927–935. 2013. View Article : Google Scholar : PubMed/NCBI

45 

Liu MY, Yue LJ, Luo YC, Lu J, Wu GD, Sheng SQ, Shi YQ and Dong ZX: SUMOylation of SIRT1 activating PGC-1alpha/PPARalpha pathway mediates the protective effect of LncRNA-MHRT in cardiac hypertrophy. Eur J Pharmacol. 930:1751552022. View Article : Google Scholar

46 

Pedram A, Razandi M, Narayanan R, Dalton JT, McKinsey TA and Levin ER: Estrogen regulates histone deacetylases to prevent cardiac hypertrophy. Mol Biol Cell. 24:3805–3818. 2013. View Article : Google Scholar : PubMed/NCBI

47 

Okabe K, Matsushima S, Ikeda S, Ikeda M, Ishikita A, Tadokoro T, Enzan N, Yamamoto T, Sada M, Deguchi H, et al: DPP (Dipeptidyl Peptidase)-4 inhibitor attenuates Ang II (Angiotensin II)-induced cardiac hypertrophy via GLP (Glucagon-Like Peptide)-1-dependent suppression of Nox (Nicotinamide Adenine Dinucleotide Phosphate Oxidase) 4-HDAC (Histone Deacetylase) 4 pathway. Hypertension. 75:991–1001. 2020. View Article : Google Scholar : PubMed/NCBI

48 

Mhatre KN, Wakula P, Klein O, Bisping E, Völkl J, Pieske B and Heinzel FR: Crosstalk between FGF23- and angiotensin II-mediated Ca(2+) signaling in pathological cardiac hypertrophy. Cell Mol Life Sci. 75:4403–4416. 2018. View Article : Google Scholar : PubMed/NCBI

49 

Fan J, Fan W, Lei J, Zhou Y, Xu H, Kapoor I, Zhu G and Wang J: Galectin-1 attenuates cardiomyocyte hypertrophy through splice-variant specific modulation of CaV1.2 calcium channel. Biochim Biophys Acta Mol Basis Dis. 1865:218–229. 2019. View Article : Google Scholar

50 

Matsushima S, Kuroda J, Ago T, Zhai P, Park JY, Xie LH, Tian B and Sadoshima J: Increased oxidative stress in the nucleus caused by Nox4 mediates oxidation of HDAC4 and cardiac hypertrophy. Circ Res. 112:651–663. 2013. View Article : Google Scholar :

51 

Zhou P, Zhao XN, Ma YY, Tang TJ, Wang SS, Wang L and Huang J: Virtual screening analysis of natural flavonoids as trimethylamine (TMA)-lyase inhibitors for coronary heart disease. J Food Biochem. 46:e143762022. View Article : Google Scholar : PubMed/NCBI

52 

Shaya GE, Leucker TM, Jones SR, Martin SS and Toth PP: Coronary heart disease risk: Low-density lipoprotein and beyond. Trends Cardiovasc Med. 32:181–194. 2022. View Article : Google Scholar

53 

Wang Y, Zhang J, Wang Z, Wang C and Ma D: Endothelial-cell-mediated mechanism of coronary microvascular dysfunction leading to heart failure with preserved ejection fraction. Heart Fail Rev. 28:169–178. 2023. View Article : Google Scholar :

54 

Yan P, Sun C, Ma J, Jin Z, Guo R and Yang B: MicroRNA-128 confers protection against cardiac microvascular endothelial cell injury in coronary heart disease via negative regulation of IRS1. J Cell Physiol. 234:13452–13463. 2019. View Article : Google Scholar : PubMed/NCBI

55 

Zhang X, Zhou H and Chang X: Involvement of mitochondrial dynamics and mitophagy in diabetic endothelial dysfunction and cardiac microvascular injury. Arch Toxicol. 97:3023–3035. 2023. View Article : Google Scholar : PubMed/NCBI

56 

Haqqani HM and Kalman JM: Aging and sinoatrial node dysfunction: Musings on the not-so-funny side. Circulation. 115:1178–1179. 2007. View Article : Google Scholar : PubMed/NCBI

57 

Mesquita T, Miguel-Dos-Santos R and Cingolani E: Aging and sinus node dysfunction: Mechanisms and future directions. Clin Sci (Lond). 139:577–593. 2025. View Article : Google Scholar : PubMed/NCBI

58 

Zhang H, Li L, Hao M, Chen K, Lu Y, Qi J, Chen W, Ren L, Cai X, Chen C, et al: Yixin-Fumai granules improve sick sinus syndrome in aging mice through Nrf-2/HO-1 pathway: A new target for sick sinus syndrome. J Ethnopharmacol. 277:1142542021. View Article : Google Scholar : PubMed/NCBI

59 

Chang X, Zhou S, Liu J, Wang Y, Guan X, Wu Q, Zhang Q, Liu Z and Liu R: Zishen Tongyang Huoxue decoction (TYHX) alleviates sinoatrial node cell ischemia/reperfusion injury by directing mitochondrial quality control via the VDAC1-β-tubulin signaling axis. J Ethnopharmacol. 320:1173712024. View Article : Google Scholar

60 

Chang X, Li Y, Liu J, Wang Y, Guan X, Wu Q, Zhou Y, Zhang X, Chen Y, Huang Y and Liu R: β-tubulin contributes to Tongyang Huoxue decoction-induced protection against hypoxia/reoxygenation-induced injury of sinoatrial node cells through SIRT1-mediated regulation of mitochondrial quality surveillance. Phytomedicine. 108:1545022023. View Article : Google Scholar

61 

Yang B, Huang Y, Zhang H, Huang Y, Zhou HJ, Young L, Xiao H and Min W: Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome. J Mol Cell Cardiol. 138:291–303. 2020. View Article : Google Scholar

62 

Chen L, Mao LS, Xue JY, Jian YH, Deng ZW, Mazhar M, Zou Y, Liu P, Chen MT, Luo G and Liu MN: Myocardial ischemia-reperfusion injury: The balance mechanism between mitophagy and NLRP3 inflammasome. Life Sci. 355:1229982024. View Article : Google Scholar : PubMed/NCBI

63 

Chang X, Zhou S, Liu J, Wang Y, Guan X, Wu Q, Liu Z and Liu R: Zishenhuoxue decoction-induced myocardial protection against ischemic injury through TMBIM6-VDAC1-mediated regulation of calcium homeostasis and mitochondrial quality surveillance. Phytomedicine. 132:1553312024. View Article : Google Scholar : PubMed/NCBI

64 

Chang X, Liu R, Li R, Peng Y, Zhu P and Zhou H: Molecular mechanisms of mitochondrial quality control in ischemic cardiomyopathy. Int J Biol Sci. 19:426–448. 2023. View Article : Google Scholar : PubMed/NCBI

65 

Wang J, Zhuang H, Jia L, He X, Zheng S, Ji K, Xie K, Ying T, Zhang Y, Li C and Chang X: Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy. Int J Biol Sci. 20:4458–4475. 2024. View Article : Google Scholar : PubMed/NCBI

66 

Pu X, Zhang Q, Liu J, Wang Y, Guan X, Wu Q, Liu Z, Liu R and Chang X: Ginsenoside Rb1 ameliorates heart failure through DUSP-1-TMBIM-6-mediated mitochondrial quality control and gut flora interactions. Phytomedicine. 132:1558802024. View Article : Google Scholar : PubMed/NCBI

67 

Zhao YT, Wang H, Zhang S, Du J, Zhuang S and Zhao TC: Irisin ameliorates hypoxia/reoxygenation-induced injury through modulation of histone deacetylase 4. PLoS One. 11:e01661822016. View Article : Google Scholar : PubMed/NCBI

68 

Lee SY and Pearce EN: Hyperthyroidism: A review. JAMA. 330:1472–1483. 2023. View Article : Google Scholar : PubMed/NCBI

69 

Kim HJ and McLeod DSA: Subclinical hyperthyroidism and cardiovascular disease. Thyroid. 34:1335–1345. 2024. View Article : Google Scholar : PubMed/NCBI

70 

Nie D, Xia C, Wang Z, Ding P, Meng Y, Liu J, Li T, Gan T, Xuan B, Huang Y, et al: CaMKII inhibition protects against hyperthyroid arrhythmias and adverse myocardial remodeling. Biochem Biophys Res Commun. 615:136–142. 2022. View Article : Google Scholar : PubMed/NCBI

71 

Diniz GP, Lino CA, Moreno CR, Senger N and Barreto-Chaves MLM: MicroRNA-1 overexpression blunts cardiomyocyte hypertrophy elicited by thyroid hormone. J Cell Physiol. 232:3360–3368. 2017. View Article : Google Scholar : PubMed/NCBI

72 

Huang ZP, Chen J, Seok HY, Zhang Z, Kataoka M, Hu X and Wang DZ: MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress. Circ Res. 112:1234–1243. 2013. View Article : Google Scholar : PubMed/NCBI

73 

Yang W, Lin J, Zhou J, Zheng Y, Jiang S, He S and Li D: Innate lymphoid cells and myocardial infarction. Front Immunol. 12:7582722021. View Article : Google Scholar : PubMed/NCBI

74 

Turkieh A, El Masri Y, Pinet F and Dubois-Deruy E: Mitophagy regulation following myocardial infarction. Cells. 11:1992022. View Article : Google Scholar : PubMed/NCBI

75 

Asensio-Lopez MC, Lax A, Del Palacio MJ, Sassi Y, Hajjar RJ, Januzzi JL, Bayes-Genis A and Pascual-Figal DA: Yin-Yang 1 transcription factor modulates ST2 expression during adverse cardiac remodeling post-myocardial infarction. J Mol Cell Cardiol. 130:216–233. 2019. View Article : Google Scholar : PubMed/NCBI

76 

Lv F, Xie L, Li L and Lin J: LMK235 ameliorates inflammation and fibrosis after myocardial infarction by inhibiting LSD1-related pathway. Sci Rep. 14:234502024. View Article : Google Scholar : PubMed/NCBI

77 

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 :

78 

Zhao J, Li L, Wang X and Shen J: KN-93 promotes HDAC4 nucleus translocation to promote fatty acid oxidation in myocardial infarction. Exp Cell Res. 438:1140502024. View Article : Google Scholar : PubMed/NCBI

79 

Hermann DM, Xin W, Bahr M, Giebel B and Doeppner TR: Emerging roles of extracellular vesicle-associated non-coding RNAs in hypoxia: Insights from cancer, myocardial infarction and ischemic stroke. Theranostics. 12:5776–5802. 2022. View Article : Google Scholar : PubMed/NCBI

80 

Li Y, Zhang Z, Zhou X, Li R, Cheng Y, Shang B, Han Y, Liu B and Xie X: Histone deacetylase 1 inhibition protects against hypoxia-induced swelling in H9c2 cardiomyocytes through regulating cell stiffness. Circ J. 82:192–202. 2017. View Article : Google Scholar : PubMed/NCBI

81 

Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC and Coats AJS: Global burden of heart failure: A comprehensive and updated review of epidemiology. Cardiovasc Res. 118:3272–3287. 2023. View Article : Google Scholar

82 

Ljubojevic-Holzer S, Herren AW, Djalinac N, Voglhuber J, Morotti S, Holzer M, Wood BM, Abdellatif M, Matzer I, Sacherer M, et al: CaMKIIdeltaC drives early adaptive Ca2+ change and late eccentric cardiac hypertrophy. Circ Res. 127:1159–1178. 2020. View Article : Google Scholar : PubMed/NCBI

83 

Lkhagva B, Lin YK, Kao YH, Chazo TF, Chung CC, Chen SA and Chen YJ: Novel histone deacetylase inhibitor modulates cardiac peroxisome proliferator-activated receptors and inflammatory cytokines in heart failure. Pharmacology. 96:184–191. 2015. View Article : Google Scholar : PubMed/NCBI

84 

Calalb MB, McKinsey TA, Newkirk S, Huynh K, Sucharov CC and Bristow MR: Increased phosphorylation-dependent nuclear export of class II histone deacetylases in failing human heart. Clin Transl Sci. 2:325–332. 2009. View Article : Google Scholar

85 

Jiang H, Jia D, Zhang B, Yang W, Dong Z, Sun X, Cui X, Ma L, Wu J, Hu K, et al: Exercise improves cardiac function and glucose metabolism in mice with experimental myocardial infarction through inhibiting HDAC4 and upregulating GLUT1 expression. Basic Res Cardiol. 115:282020. View Article : Google Scholar : PubMed/NCBI

86 

Dzau VJ and Hodgkinson CP: Precision hypertension. Hypertension. 81:702–708. 2024. View Article : Google Scholar

87 

Kanbay M, Copur S, Tanriover C, Ucku D and Laffin L: Future treatments in hypertension: Can we meet the unmet needs of patients? Eur J Intern Med. 115:18–28. 2023. View Article : Google Scholar : PubMed/NCBI

88 

Laurent S, Alivon M, Beaussier H and Boutouyrie P: Aortic stiffness as a tissue biomarker for predicting future cardiovascular events in asymptomatic hypertensive subjects. Ann Med. 44(Suppl 1): S93–S97. 2012. View Article : Google Scholar : PubMed/NCBI

89 

Usui T, Okada M, Mizuno W, Oda M, Ide N, Morita T, Hara Y and Yamawaki H: HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats. Am J Physiol Heart Circ Physiol. 302:H1894–H1904. 2012. View Article : Google Scholar : PubMed/NCBI

90 

Kim GR, Cho SN, Kim HS, Yu SY, Choi SY, Ryu Y, Lin MQ, Jin L, Kee HJ and Jeong MH: Histone deacetylase and GATA-binding factor 6 regulate arterial remodeling in angiotensin II-induced hypertension. J Hypertens. 34:2206–2219. 2016. View Article : Google Scholar : PubMed/NCBI

91 

Saigusa R, Winkels H and Ley K: T cell subsets and functions in atherosclerosis. Nat Rev Cardiol. 17:387–401. 2020. View Article : Google Scholar : PubMed/NCBI

92 

Chen F, Li J, Zheng T, Chen T and Yuan Z: KLF7 alleviates atherosclerotic lesions and inhibits glucose metabolic reprogramming in macrophages by regulating HDAC4/miR-148b-3p/NCOR1. Gerontology. 68:1291–1310. 2022. View Article : Google Scholar : PubMed/NCBI

93 

Zhu XX, Meng XY, Chen G, Sru JB, Fu X, Xu AJ, Liu Y, Hou XH, Qiu HB, Sun QY, et al: Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling. Cell Commun Signal. 22:4882024. View Article : Google Scholar : PubMed/NCBI

94 

Zhao X, Liu S, Wang X, Chen Y, Pang P, Yang Q, Lin J, Deng S, Wu S, Fan G and Wang B: Diabetic cardiomyopathy: Clinical phenotype and practice. Front Endocrinol (Lausanne). 13:10322682022. View Article : Google Scholar : PubMed/NCBI

95 

Ma X, Mei S, Wuyun Q, Zhou L, Sun D and Yan J: Epigenetics in diabetic cardiomyopathy. Clin Epigenetics. 16:522024. View Article : Google Scholar : PubMed/NCBI

96 

Kronlage M, Dewenter M, Grosso J, Fleming T, Oehl U, Lehmann LH, Falcão-Pires I, Leite-Moreira AF, Volk N, Gröne HJ, et al: O-GlcNAcylation of histone deacetylase 4 protects the diabetic heart from failure. Circulation. 140:580–594. 2019. View Article : Google Scholar : PubMed/NCBI

97 

Heymans S, Lakdawala NK, Tschope C and Klingel K: Dilated cardiomyopathy: Causes, mechanisms, and current and future treatment approaches. Lancet. 402:998–1011. 2023. View Article : Google Scholar : PubMed/NCBI

98 

Castillero E, Ali ZA, Akashi H, Giangreco N, Wang C, Stöhr EJ, Ji R, Zhang X, Kheysin N, Park JS, et al: Structural and functional cardiac profile after prolonged duration of mechanical unloading: Potential implications for myocardial recovery. Am J Physiol Heart Circ Physiol. 315:H1463–H1476. 2018. View Article : Google Scholar : PubMed/NCBI

99 

Lu D, Bao D, Dong W, Liu N, Zhang X, Gao S, Ge W, Gao X and Zhang L: Dkk3 prevents familial dilated cardiomyopathy development through Wnt pathway. Lab Invest. 96:239–248. 2016. View Article : Google Scholar

100 

Li T, Mu N, Yin Y, Yu L and Ma H: Targeting AMP-activated protein kinase in aging-related cardiovascular diseases. Aging Dis. 11:967–977. 2020. View Article : Google Scholar : PubMed/NCBI

101 

Tyrrell DJ and Goldstein DR: Ageing and atherosclerosis: Vascular intrinsic and extrinsic factors and potential role of IL-6. Nat Rev Cardiol. 18:58–68. 2021. View Article : Google Scholar

102 

Saravi SS and Feinberg MW: Can removal of zombie cells revitalize the aging cardiovascular system? Eur Heart J. 45:867–869. 2024. View Article : Google Scholar

103 

Shabanian K, Shabanian T, Karsai G, Pontiggia L, Paneni F, Ruschitzka F, Beer JH and Saravi SS: AQP1 differentially orchestrates endothelial cell senescence. Redox Biol. 76:1033172024. View Article : Google Scholar : PubMed/NCBI

104 

Bhatt DL, Lopes RD and Harrington RA: Diagnosis and treatment of acute coronary syndromes: A review. JAMA. 327:662–675. 2022. View Article : Google Scholar : PubMed/NCBI

105 

Xu H, Zhang J, Jia H, Xing F and Cong H: Serum histone deacetylase 4 longitudinal change for estimating major adverse cardiovascular events in acute coronary syndrome patients receiving percutaneous coronary intervention. Ir J Med Sci. 192:2689–2696. 2023. View Article : Google Scholar : PubMed/NCBI

106 

Kang Y, Kim J, Anderson JP, Wu J, Gleim SR, Kundu RK, McLean DL, Kim JD, Park H, Jin S, et al: Apelin-APJ signaling is a critical regulator of endothelial MEF2 activation in cardiovascular development. Circ Res. 113:22–31. 2013. View Article : Google Scholar : PubMed/NCBI

107 

Helmstadter KG, Ljubojevic-Holzer S, Wood BM, Taheri KD, Sedej S, Erickson JR, Bossuyt J and Bers DM: CaMKII and PKA-dependent phosphorylation co-regulate nuclear localization of HDAC4 in adult cardiomyocytes. Basic Res Cardiol. 116:112021. View Article : Google Scholar : PubMed/NCBI

108 

Li Y, Yu J, Li R, Zhou H and Chang X: New insights into the role of mitochondrial metabolic dysregulation and immune infiltration in septic cardiomyopathy by integrated bioinformatics analysis and experimental validation. Cell Mol Biol Lett. 29:212024. View Article : Google Scholar : PubMed/NCBI

109 

Chang X, Zhang Q, Huang Y, Liu J, Wang Y, Guan X, Wu Q, Liu Z and Liu R: Quercetin inhibits necroptosis in cardiomyocytes after ischemia-reperfusion via DNA-PKcs-SIRT5-orchestrated mitochondrial quality control. Phytother Res. 38:2496–2517. 2024. View Article : Google Scholar : PubMed/NCBI

110 

Wang J, Zhuang H, Yang X, Guo Z, Zhou K, Liu N, An Y, Chen Y, Zhang Z, Wang M, et al: Exploring the mechanism of ferroptosis induction by sappanone A in cancer: Insights into the mitochondrial dysfunction mediated by NRF2/xCT/GPX4 axis. Int J Biol Sci. 20:5145–5161. 2024. View Article : Google Scholar : PubMed/NCBI

111 

Pang B, Dong G, Pang T, Sun X, Liu X, Nie Y and Chang X: Emerging insights into the pathogenesis and therapeutic strategies for vascular endothelial injury-associated diseases: Focus on mitochondrial dysfunction. Angiogenesis. 27:623–639. 2024. View Article : Google Scholar : PubMed/NCBI

112 

Du J, Zhang L, Zhuang S, Qin GJ and Zhao TC: HDAC4 degradation mediates HDAC inhibition-induced protective effects against hypoxia/reoxygenation injury. J Cell Physiol. 230:1321–1331. 2015. View Article : Google Scholar :

113 

Marek L, Hamacher A, Hansen FK, Kuna K, Gohlke H, Kassack MU and Kurz T: Histone deacetylase (HDAC) inhibitors with a novel connecting unit linker region reveal a selectivity profile for HDAC4 and HDAC5 with improved activity against chemoresistant cancer cells. J Med Chem. 56:427–436. 2013. View Article : Google Scholar

114 

Chen M, Cheng H, Chen X, Gu J, Su W, Cai G, Yan Y, Wang C, Xia X, Zhang K, et al: The activation of histone deacetylases 4 prevented endothelial dysfunction: A crucial mechanism of HuangqiGuizhiWuwu decoction in improving microcirculation dysfunction in diabetes. J Ethnopharmacol. 307:1162402023. View Article : Google Scholar : PubMed/NCBI

115 

Choi SY, Kee HJ, Sun S, Seok YM, Ryu Y, Kim GR, Kee SJ, Pflieger M, Kurz T, Kassack MU and Jeong MH: Histone deacetylase inhibitor LMK235 attenuates vascular constriction and aortic remodelling in hypertension. J Cell Mol Med. 23:2801–2812. 2019. View Article : Google Scholar : PubMed/NCBI

116 

Lkhagva B, Chang SL, Chen YC, Kao YH, Lin YK, Chiu CT, Chen SA and Chen YJ: Histone deacetylase inhibition reduces pulmonary vein arrhythmogenesis through calcium regulation. Int J Cardiol. 177:982–989. 2014. View Article : Google Scholar : PubMed/NCBI

117 

Chen Y, Yuan J, Jiang G, Zhu J, Zou Y and Lv Q: Lercanidipine attenuates angiotensin II-induced cardiomyocyte hypertrophy by blocking calcineurin-NFAT3 and CaMKII-HDAC4 signaling. Mol Med Rep. 16:4545–4552. 2017. View Article : Google Scholar : PubMed/NCBI

118 

Wang S, Li J, Liu Y, Zhang J, Zheng X, Sun X, Lei S, Kang Z, Chen X, Lei M, et al: Distinct roles of calmodulin and Ca(2+)/calmodulin-dependent protein kinase II in isopreterenol-induced cardiac hypertrophy. Biochem Biophys Res Commun. 526:960–966. 2020. View Article : Google Scholar : PubMed/NCBI

119 

Sun H, Ling S, Zhao D, Li Y, Zhong G, Guo M, Li Y, Yang L, Du J, Zhou Y, et al: Panax quinquefolium saponin attenuates cardiac remodeling induced by simulated microgravity. Phytomedicine. 56:83–93. 2019. View Article : Google Scholar : PubMed/NCBI

120 

Liu F, Su H, Liu B, Mei Y, Ke Q, Sun X and Tan W: STVNa attenuates isoproterenol-induced cardiac hypertrophy response through the HDAC4 and Prdx2/ROS/Trx1 pathways. Int J Mol Sci. 21:6822020. View Article : Google Scholar : PubMed/NCBI

121 

Akbay B, Omarova Z, Trofimov A, Sailike B, Karapina O, Molnár F and Tokay T: Double-Edge effects of leucine on cancer cells. Biomolecules. 14:14012024. View Article : Google Scholar : PubMed/NCBI

122 

Dulf PL, Coada CA, Florea A, Moldovan R, Baldea I, Dulf DV, Blendea D and Filip AG: Mitigating doxorubicin-induced cardiotoxicity through quercetin intervention: An experimental study in rats. Antioxidants (Basel). 13:10682024. View Article : Google Scholar : PubMed/NCBI

123 

Zhang W, Zheng Y, Yan F, Dong M and Ren Y: Research progress of quercetin in cardiovascular disease. Front Cardiovasc Med. 10:12037132023. View Article : Google Scholar : PubMed/NCBI

124 

Lin CY, Shibu MA, Wen R, Day CH, Chen RJ, Kuo CH, Ho TJ, Viswanadha VP, Kuo WW and Huang CY: Leu(27) IGF-II-induced hypertrophy in H9c2 cardiomyoblasts is ameliorated by saffron by regulation of calcineurin/NFAT and CaMKIIδ signaling. Environ Toxicol. 36:2475–2483. 2021. View Article : Google Scholar : PubMed/NCBI

125 

Sehgel NL, Zhu Y, Sun Z, Trzeciakowski JP, Hong Z, Hunter WC, Vatner DE, Meininger GA and Vatner SF: Increased vascular smooth muscle cell stiffness: A novel mechanism for aortic stiffness in hypertension. Am J Physiol Heart Circ Physiol. 305:H1281–H1287. 2013. View Article : Google Scholar : PubMed/NCBI

126 

Choi SY, Kee HJ, Jin L, Ryu Y, Sun S, Kim GR and Jeong MH: Inhibition of class IIa histone deacetylase activity by gallic acid, sulforaphane, TMP269, and panobinostat. Biomed Pharmacother. 101:145–154. 2018. View Article : Google Scholar : PubMed/NCBI

127 

Xiang Z, Guan H, Zhao X, Xie Q, Xie Z, Cai F, Dang R, Li M and Wang C: Dietary gallic acid as an antioxidant: A review of its food industry applications, health benefits, bioavailability, nano-delivery systems, and drug interactions. Food Res Int. 180:1140682024. View Article : Google Scholar : PubMed/NCBI

128 

Hadidi M, Linan-Atero R, Tarahi M, Christodoulou MC and Aghababaei F: The potential health benefits of gallic acid: Therapeutic and food applications. Antioxidants (Basel). 13:10012024. View Article : Google Scholar : PubMed/NCBI

129 

Ago T, Yang Y, Zhai P and Sadoshima J: Nifedipine inhibits cardiac hypertrophy and left ventricular dysfunction in response to pressure overload. J Cardiovasc Transl Res. 3:304–313. 2010. View Article : Google Scholar : PubMed/NCBI

130 

Guo YJ, Yao JJ, Guo ZZ, Ding M, Zhang KL, Shen QH, Li Y, Yu SF, Wan T, Xu FP, et al: HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis. Acta Pharmacol Sin. 45:1224–1236. 2024. View Article : Google Scholar : PubMed/NCBI

131 

Tucker WJ, Fegers-Wustrow I, Halle M, Haykowsky MJ, Chung EH and Kovacic JC: Exercise for primary and secondary prevention of cardiovascular disease: JACC focus seminar 1/4. J Am Coll Cardiol. 80:1091–1106. 2022. View Article : Google Scholar : PubMed/NCBI

132 

Wang Y, Yuan J, Liu H, Chen J, Zou J, Zeng X, Du L, Sun X, Xia Z, Geng Q, et al: Elevated meteorin-like protein from high-intensity interval training improves heart function via AMPK/HDAC4 pathway. Genes Dis. 11:1011002024. View Article : Google Scholar : PubMed/NCBI

133 

Chen Y, Liu J, Zhang Q, Chai L, Chen H, Li D, Wang Y, Qiu Y, Shen N, Zhang J, et al: Activation of CaMKII/HDAC4 by SDF1 contributes to pulmonary arterial hypertension via stabilization Runx2. Eur J Pharmacol. 970:1764832024. View Article : Google Scholar : PubMed/NCBI

134 

Xiong C and Yang B: Revising the hemodynamic criteria for pulmonary hypertension: A perspective from China. J Transl Int Med. 11:1–3. 2023. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma X, Wei R, Song A, Zhang X, Zou J and Hao S: Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review). Int J Mol Med 56: 158, 2025.
APA
Ma, X., Wei, R., Song, A., Zhang, X., Zou, J., & Hao, S. (2025). Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review). International Journal of Molecular Medicine, 56, 158. https://doi.org/10.3892/ijmm.2025.5599
MLA
Ma, X., Wei, R., Song, A., Zhang, X., Zou, J., Hao, S."Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review)". International Journal of Molecular Medicine 56.4 (2025): 158.
Chicago
Ma, X., Wei, R., Song, A., Zhang, X., Zou, J., Hao, S."Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 158. https://doi.org/10.3892/ijmm.2025.5599
Copy and paste a formatted citation
x
Spandidos Publications style
Ma X, Wei R, Song A, Zhang X, Zou J and Hao S: Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review). Int J Mol Med 56: 158, 2025.
APA
Ma, X., Wei, R., Song, A., Zhang, X., Zou, J., & Hao, S. (2025). Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review). International Journal of Molecular Medicine, 56, 158. https://doi.org/10.3892/ijmm.2025.5599
MLA
Ma, X., Wei, R., Song, A., Zhang, X., Zou, J., Hao, S."Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review)". International Journal of Molecular Medicine 56.4 (2025): 158.
Chicago
Ma, X., Wei, R., Song, A., Zhang, X., Zou, J., Hao, S."Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 158. https://doi.org/10.3892/ijmm.2025.5599
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team