Molecular biological and immunological analysis for the relationship between periodontal disease and atherosclerosis

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Is has been postulated that periodontal infection may be involved in the initiation and progression of atherosclerosis and subsequent coronary heart disease. Although this concept has been supported by epidemiological case control studies, biological relevance of periodontitis to initiation and progression of atherosclerosis remained unknown. In this research project we analyzed the effects of bacterial antigens and inflammatory cytokines synthesized in the periodontitis lesion on endothelial cell function and the role of humoral and cellular immune responses to bacterial antigen and cross-reactive endogenous antigen on the atherogenesis. Lipopolysaccharide (LPS) and GroEL (HSP60) from Porphyromonas gingivalis (P.gingivalis), a representative periodontopathic bacterium, up-regulated the expression of ICAM-1 and VCAM-a on human coronary arterial endothelial cells. IL-1b and TNF-a, both of which are involved in the tissue destruction seen in periodontitis, also up-regulated the expression of these molecules at concentrations seen in the sera of periodontitis patients. Despite being highly homologous between prokaryotic and eukaryotic cells, HSP60s are strongly immunogenic and are thought to implicate in inflammation as well as the autoimmune diseases. Antibody levels to both human and P.gingivalis HSP60s were the highest in atherosclerosis patients followed by periodontitis patients and healthy subjects. Clonal analysis of the T cells clearly demonstrated the presence of not only human HSP60-but also P.gingivalis GroEL-reactive T-cell populations in the peripheral circulation of atherosclerosis patients. Furthermore, these HSP60-reactive T cells seemed to be present in atherosclerotic lesions in some patients. These results clearly indicate that periodontal infection has the potential to affect human coronary arterial endothelial cells and may contribute to the development of subsequent atherosclerosis.