PAMPs and DAMPs as the Bridge Between Periodontitis and Atherosclerosis: The Potential Therapeutic Targets

Abstract

Atherosclerosis is a chronic artery disease characterized by plaque formation and vascular inflammation, eventually leading to myocardial infarction and stroke. Innate immunity plays an irreplaceable role in the vascular inflammatory response triggered by chronic infection. Periodontitis is a common chronic disorder that involves oral microbe-related inflammatory bone loss and local destruction of the periodontal ligament and is a risk factor for atherosclerosis. Periodontal pathogens contain numerous pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide, CpG DNA, and Peptidoglycan, that initiate the inflammatory response of the innate immunity depending on the recognition of pattern-recognition receptors (PRRs) of host cells. The immune-inflammatory response and destruction of the periodontal tissue will produce a large number of damage-associated molecular patterns (DAMPs) such as neutrophil extracellular traps (NETs), high mobility group box 1 (HMGB1), alarmins (S100 protein), and which can further affect the progression of atherosclerosis. Molecular patterns have recently become the therapeutic targets for inflammatory disease, including blocking the interaction between molecular patterns and PRRs and controlling the related signal transduction pathway. This review summarized the research progress of some representative PAMPs and DAMPs as the molecular pathological mechanism bridging periodontitis and atherosclerosis. We also discussed possible ways to prevent serious cardiovascular events in patients with periodontitis and atherosclerosis by targeting molecular patterns.

Keywords: DAMPs; PAMPs; PRRs; atherosclerosis; innate immunity; periodontitis.

FIGURE 1

Periodontitis mediates the formation of atherosclerosis by producing PAMPs and DAMPs. Periodontal pathogens produce PAMPs, including LPS, PGN, and CpG DNA. Periodontal infection activates neutrophils to form NETs, which together with HMGB1 and alarmins released by damaged periodontal cells constitute DAMPs. PAMPs and DAMPs activate excessive innate immunity by acting on TLRs and NLRs in arterial tissue, leading to foam cell formation, endothelial cell and vascular smooth muscle cell dysfunction, and promoting the massive release of inflammatory factors, which are involved in the regulation of AS.