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Review Open Access

Association between periodontitis and heart failure: Mechanisms and clinical implications (Review)

  • Authors:
    • Xinyue Zhang
    • Xiaoli An
  • View Affiliations / Copyright

    Affiliations: School of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 263
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    Published online on: July 28, 2026
       https://doi.org/10.3892/mmr.2026.13974
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Abstract

Periodontitis, a common oral disease, is increasingly recognized for its potential impact on systemic health, particularly its association with heart failure (HF). HF is a complex clinical syndrome with a multifactorial pathogenesis. Emerging evidence suggests that periodontitis may influence the cardiovascular system and contribute to the onset and progression of HF through mechanisms such as systemic inflammation, microbial shifts, and immune dysregulation. However, current research still faces limitations in establishing causality and elucidating the precise underlying mechanisms. Furthermore, clinical intervention strategies require further investigation. Relevant literature was identified from PubMed, Web of Science, and Scopus using keywords related to periodontitis and heart failure, and screened for relevance to epidemiological evidence, mechanistic insights, and clinical implications. The present review aimed to summarize the mechanisms linking periodontitis and HF, analyze their shared pathophysiological basis, and discuss the potential role of periodontal treatment in improving outcomes for patients with HF. Clinically, periodontal assessment may be considered in patients with heart failure as part of multidisciplinary care, but current evidence remains insufficient to support definitive recommendations that such evaluation or treatment improves HF outcomes.
View Figures

Figure 1

Schematic overview of the core
mechanisms linking periodontitis to the pathogenesis of heart
failure (‘the periodontal-cardiac axis’). Periodontitis, a chronic
localized infection, can systemically impact cardiac function and
contribute to the development or exacerbation of heart failure
through three primary pathways: i) Systemic inflammation:
Pathogen-associated molecular patterns, such as lipopolysaccharide
released from periodontal pathogens (for example, Porphyromonas
gingivalis), enter the systemic circulation. This triggers a
widespread inflammatory response characterized by elevated levels
of pro-inflammatory cytokines (such as IL-6, TNF-α, and IL-1β).
These mediators can directly target cardiomyocytes and cardiac
fibroblasts, inducing apoptosis and myocardial fibrosis, which
leads to adverse ventricular remodeling and cardiac dysfunction.
Concurrently, they can act on hematopoietic stem and progenitor
cells in the bone marrow, inducing epigenetic reprogramming and a
state of ‘trained immunity,’ which generates hyper-responsive
myeloid cells that perpetuate systemic inflammation. ii) Microbial
dissemination: Periodontal pathogens can directly invade the
bloodstream via transient bacteremia. These bacteria and their
virulence factors (such as gingipains) may colonize cardiac tissues
or the vasculature, or exert direct cardiotoxic effects, impairing
cardiomyocyte function and endothelial integrity. iii) Immune
cross-reactivity: Due to molecular mimicry between certain antigens
from periodontal pathogens and host cardiac proteins (such as
cardiac myosin), antibodies generated against the pathogens may
cross-react with self-antigens in the heart, leading to
autoimmune-mediated cardiac injury. Furthermore, shared risk
factors, such as genetic susceptibility and metabolic syndrome, can
predispose individuals to both periodontitis and heart failure,
contributing to the complex pathogenic network of the
‘periodontal-cardiac axis.’

Figure 2

Cellular and molecular pathways of
systemic inflammation-driven cardiac injury. Systemic inflammation
induced by periodontitis mediates cardiac damage through two
synergistic pathways: i) Upstream trigger and signal amplification:
LPS released from periodontal lesions enters the circulation and is
recognized by TLR4 on the surface of immune cells, such as
macrophages. This binding activates key intracellular inflammatory
signaling cascades, primarily NF-κB and mitogen-activated protein
kinase pathways. Activated immune cells then produce and release
large quantities of pro-inflammatory cytokines (such as IL-6,
TNF-α, and IL-1β) into the bloodstream, amplifying a local
infection into a systemic inflammatory state. ii) Downstream
effects: The elevated levels of circulating inflammatory mediators
inflict cardiac damage through two principal pathways. Pathway A:
Direct cardiac injury: Pro-inflammatory cytokines directly target
cardiomyocytes, activating apoptotic programs (for example, via
caspase cascades) and leading to cell death. Concurrently, they
stimulate cardiac fibroblasts to proliferate and differentiate,
promoting excessive extracellular matrix deposition and culminating
in myocardial fibrosis. Together, apoptosis and fibrosis drive
adverse ventricular remodeling and impair cardiac function. Pathway
B: Myeloid reprogramming and trained immunity: Circulating
cytokines, particularly IL-1β, can act on HSPCs within the bone
marrow. By inducing epigenetic reprogramming (for example, histone
modifications), these cytokines skew hematopoiesis toward the
myeloid lineage, generating functionally ‘trained’ and
hyper-responsive monocytes/macrophages. These ‘trained immunity’
cells mount an exaggerated inflammatory response upon secondary
stimulation, creating a vicious cycle that perpetuates and
amplifies inflammatory damage to the cardiovascular system. LPS,
lipopolysaccharide; HSPCs, hematopoietic stem and progenitor
cells.

Figure 3

Primary three mechanisms of remote
cardiac injury driven by the periodontal microbiota. In addition to
indirectly affecting the heart via inflammatory mediators, the
periodontal microbiota and its products can actively participate in
cardiac pathology through three distinct pathways. i) Direct
dissemination: During daily activities (for example, chewing or
toothbrushing) or dental procedures, pathogens within the
periodontal pocket (notably Porphyromonas gingivalis) can
breach the compromised periodontal tissue barrier, leading to
transient bacteremia. These circulating bacteria can survive in the
bloodstream and subsequently colonize distant sites such as heart
valves, myocardial tissue, or coronary atherosclerotic plaques,
where they can directly induce local inflammation and tissue
damage. ii) Remote effects of virulence factors: Even if the
bacteria themselves do not survive in circulation, their potent
secreted virulence factors can enter the bloodstream and exert
remote biological effects. For example, gingipains, a class of
proteases produced by Porphyromonas gingivalis, can degrade
intercellular junction proteins (for example, VE-cadherin) in the
vascular endothelium, compromising vascular barrier integrity.
Furthermore, they can directly target cardiomyocytes, interfering
with critical cellular functions such as autophagy and exerting
direct cardiotoxicity. iii) Disruption of the oral-gut axis:
Patients with periodontitis continuously swallow saliva containing
a high load of periodontal pathogens. These microbes can survive
the gastric acid barrier and reach the intestines, altering the
composition and function of the intestinal microbiota and causing
gut dysbiosis. This dysbiosis can impair the integrity of the
intestinal mucosal barrier, leading to increased intestinal
permeability (‘leaky gut’). This allows a greater translocation of
bacterial products (for example, LPS) from the gut lumen into the
circulation, thereby indirectly amplifying the systemic
inflammatory burden and contributing to cardiac damage.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang X and An X: Association between periodontitis and heart failure: Mechanisms and clinical implications (Review). Mol Med Rep 34: 263, 2026.
APA
Zhang, X., & An, X. (2026). Association between periodontitis and heart failure: Mechanisms and clinical implications (Review). Molecular Medicine Reports, 34, 263. https://doi.org/10.3892/mmr.2026.13974
MLA
Zhang, X., An, X."Association between periodontitis and heart failure: Mechanisms and clinical implications (Review)". Molecular Medicine Reports 34.4 (2026): 263.
Chicago
Zhang, X., An, X."Association between periodontitis and heart failure: Mechanisms and clinical implications (Review)". Molecular Medicine Reports 34, no. 4 (2026): 263. https://doi.org/10.3892/mmr.2026.13974
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang X and An X: Association between periodontitis and heart failure: Mechanisms and clinical implications (Review). Mol Med Rep 34: 263, 2026.
APA
Zhang, X., & An, X. (2026). Association between periodontitis and heart failure: Mechanisms and clinical implications (Review). Molecular Medicine Reports, 34, 263. https://doi.org/10.3892/mmr.2026.13974
MLA
Zhang, X., An, X."Association between periodontitis and heart failure: Mechanisms and clinical implications (Review)". Molecular Medicine Reports 34.4 (2026): 263.
Chicago
Zhang, X., An, X."Association between periodontitis and heart failure: Mechanisms and clinical implications (Review)". Molecular Medicine Reports 34, no. 4 (2026): 263. https://doi.org/10.3892/mmr.2026.13974
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