Periodontal disease is a bacterial infection of the gums, which can lead to tooth loss. In some patients, periodontal disease represents a chronic infection, and may lead to systemic complications. Because atherosclerosis is caused by chronic inflammation, the hypothesis that a causal link between periodontal disease and atherosclerosis has been proposed. Previous epidemiologic and experimental research supports an association between periodontal disease and atherosclerosis. Chronic inflammatory states and atherosclerosis are further characterized by increased risk of blood clots (thrombosis). Understanding the mechanism(s) of accelerated atherosclerosis and the pro-thrombotic phenotype associated with periodontal disease would provide insight into therapeutic strategies with significant public health ramifications. We recently uncovered a pro-thrombotic role for the class B scavenger receptor, CD36, on platelets, and previously demonstrated that it is pro-atherogenic. We hypothesize that periodontal disease leads to accelerated atherosclerosis by increasing inflammation and associated oxidant stress. Furthermore, we hypothesize that inflammation/oxidant stress is essential to the creation of a CD36 dependent pro-atherogenic and pro-thrombotic state. The goal of this application is to use the western diet fed LDLRo mouse model to determine if periodontal disease-dependent accelerated atherosclerosis and increased thrombotic risk are CD36- dependent. The ultimate goal of this work is to determine if CD36 specifically contributes to these pathologies such that future therapeutic regimens can be appropriately tailored to patients with specific risk factors of disease.
Conditions which increase inflammation may increase the likelihood of atherosclerosis and thrombosis by creating CD36 interacting molecules. We believe that inflammation caused by periodontitis may be one such condition. Our work is relevant to disease states that are highly prevalent in the general population and thus can widely impact public health.
|Brown, Paul M; Kennedy, David J; Morton, Richard E et al. (2015) CD36/SR-B2-TLR2 Dependent Pathways Enhance Porphyromonas gingivalis Mediated Atherosclerosis in the Ldlr KO Mouse Model. PLoS One 10:e0125126|