These data highlight the concept that a key common denominator in infected periodontium and diabetic blood vessels is enhanced inflammation. Our findings on the role of RAGE blockade in attenuating inflammation and tissue injury in both settings place RAGE at the center of a cascade of systemic/local inflammatory conditions that may accelerate microvascular dysfunction. We thus propose that peri-odontal disease presents a sufficient stimulus to augment both local and systemic vascular activation—processes that, if left unchecked, may predispose to acceleration of atherosclerosis. In the setting of diabetes, however, inflammation in local and vascular tissues is further fueled, at least in part via ligation of RAGE, by accumulation of AGEs, proin-flammatory molecules such as S100/calgranulins, and oxi-dant species.
Taken together, these considerations underscore the premise that control of the exaggerated inflammatory response in bacterial infection of the periodontium and in the diabetic vessel wall may provide therapeutic benefit in vascular disease and atherosclerosis.
Advanced glycation end products: Products of nonenzymatic glyca-tion and oxidation of proteins and lipids; these species may be formed by such stimuli as hyperglycemia, inflammation, and oxidant stress.
Flow-mediated dilation: Measure of endothelial function and the bioavailability/activity of nitric oxide; flow-mediated dilation is generally measured by assessment of blood flow in the brachial artery by ultrasonography.
Periodontium: The tissues that invest and support the teeth including the gingiva, cementum (covering the roots), alveolar bone, and periodontal ligament (the ligament that attaches the tooth to the bone).
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Evanthia Lalla, an Associate Professor of Dentistry at Columbia University, has been studying mechanisms underlying the association between diabetes, atherosclerosis, and periodontal infections.
Panos N. Papapanou and Ira B. Lamster are Professors of Dentistry at Columbia University and established investigators in the fields of epidemiology and pathogenesis of periodontal diseases.
Ann Marie Schmidt is a Professor of Surgery. Her laboratory primarily focuses on vascular biology and the receptor for advanced glycation end products.
Their work is supported by grants from the NIH, JDRFI, AHA, and Burroughs Wellcome Fund.
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