PD Dr. med. Nikos Werner
Department of Internal Medicine II, Cardiology, Pneumology, and Angiology
University of Bonn
PD Dr. med. dent. Moritz Kebschull
Department of Periodontology, Operative and Preventive Dentistry
University of Bonn
First Funding Period
Impact of periodontitis on vascular damage and regeneration
Besides local inflammation, periodontitis is also associated with systemic inflammatory reactions. Inflammatory processes play an important role in the pathogenesis of atherosclerosis. Besides inflammatory processes, increased endothelial cell apoptosis and diminished endothelial cell regeneration by endothelial progenitor cells (EPCs) are thought to be relevant for the pathogenesis of endothelial dysfunction, an early and crucial stage of atherogenesis associated with an adverse prognosis, and atherosclerosis. Recent clinical and epidemiological investigations demonstrated that severe periodontitis causes endothelial dysfunction and may be associated with coronary artery disease and an increased cardiovascular event rate. The molecular and cellular mechanisms are incompletely understood at present. The relevance of endothelial cell apoptosis and EPCs in this context is unknown. The aim of this project is to elucidate the impact of periodontitis on vascular damage and repair and the role of vascular regeneration in the treatment of periodontitis. For that purpose, cell culture and animal experiments and clinical investigations in humans will be performed. This will possibly help to establish new strategies for the treatment of periodontal disease that may improve local treatment success and in addition decrease the cardiovascular risk of the diseased individual.
Second Funding Period
Periodontal infections and stem cell mobilization in atherosclerosis
Periodontitis has been closely connected to cardiovascular disease. However, the underlying common pathways remain incompletely understood. Vascular health is maintained by healthy endothelium that can in parts be regenerated by circulating endothelial-regenerating cells (e.g. Sca1+/flk1+ progenitors). Impaired endothelial regeneration after endothelial cell damage is closely connected to the development of atherosclerotic lesions. We have demonstrated that experimental periodontitis in atherosclerosis-prone ApoE-deficient mice leads to defective progenitor cell mobilization into peripheral blood (PB). Mechanistically, osteoclast activation, mediated by receptor activator of nuclear factor B ligand (RANKL), is associated with progenitor cell mobilization whilst osteoprotegerin (OPG), a decoy receptor for RANKL, triggers stem cell expansion and retention within the BM via increased osteogenesis. We showed that periodontal infections are associated with a concomitant increase in OPG and a decreased RANKL/OPG ratio – inverse of the situation in the periodontal tissues. Interestingly, OPG is an established surrogate marker of atherosclerosis and predicts cardiovascular mortality. Therefore, the alteration of BM cell mobilization by periodontal infections may constitute a novel mechanistic link to atherosclerosis.
We herein propose to elicit the exact mechanisms by which periodontal infections influence cell mobilization from the bone marrow, and to explore the functional relevance of decreased mobilization in chronic periodontal infections.