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

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  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…

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  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…

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  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,…