Periodontal associations in cardiovascular diseases: The latest evidence and understanding

Abstract

Periodontal and cardiovascular diseases (CVD) are inflammatory diseases. Recent epidemiological studies have associated the effect of periodontitis on CVD progression. Findings of oral pathogens in carotid atheromas provided a plausible relationship between these two diseases. One possible mechanism is the infiltration of oral/periodontal pathogens through inflamed and ulcerated gingival epithelium. This results in translocation of oral pathogens throughout the systemic circulation affecting vascular tissues, and initiating a cascade of inflammatory reactions detrimental to the cardiovascular system. In addition, leakage of pro-inflammatory cytokines/chemokines from the ulcerated periodontium into the bloodstream may cause the production of hepatic acute-phase proteins. Moreover, as chronic bacteremia occurs, the adaptive immune system is activated. Antibodies produced in response to periodontal pathogens trigger a cross-reaction between endothelial cells and modified low-density lipoprotein to enhance the movement of lipids into cells within the vessel wall. Some antibodies and inflammatory cytokines promote the Th1 response, thereby further activating macrophages within the atheroma. These plausible mechanisms are contributing factors in initiating and propagating atherogenesis. This review discusses the current understanding of CVD pathology/periodontitis, potential underlying mechanisms regarding this association, and general guidelines for treating patients with CVD risks.

Keywords: Cardiovascular diseases; Inflammatory cytokines; Oral pathogens; Periodontal disease; Systemic inflammation.

Fig. 1

The biologically plausible mechanisms for periodontitis as a risk factor for atherogenesis. There are two pathways that can occur simultaneously by which periodontal infection can affect atherogenesis. In the direct pathway, bacteria infiltrate into the systemic circulation (circle 2) from chronic periodontal infection (shown by circle 1) and penetrate the vascular endothelium causing injury. This in turn triggers the host's inflammatory response, thereby causing the acute-phase response, dyslipidemia (circle 3a) and activation of the adaptive immune system (circle 3b). Plasma cells recognizing the Pathogen associated molecular patterns (PAMPs) of the circulating bacteria release antibodies that can cross react with endothelium and LDL causing more lipids to migrate into endothelial cells (circle 3b). In addition, released antibodies can trigger the Th1 response and enhance macrophage proliferation and migration (circle 3b). In the indirect pathway, bacterial endotoxins and/or pro-inflammatory cytokines disseminate in the bloodstream (circle 2). Similar to the direct pathway, the circulation of these peptides triggers inflammation (IL-1, IL-6, TNFα, PGE2). In response, the liver initiates an acute-phase response, releasing CRP, fibrinogen, amyloid A protein, and many other mediators into circulation (circle 3a). In addition, there is an increase in cholesterol synthesis as a disruption in lipid balance occurs. Furthermore, the chemokines released from the bacteria target leukocytes and lymphocytes from both the innate and adaptive immune systems and initiate cell migration and activity. In response, antibodies are released into circulation (circle 3b) and there is an upregulation of macrophages. Both pathways, direct and indirect, lead to Atherogenesis and/or exacerbation of atherothrombotic lesions (circle 4).