McAllister Heart Institute Seminar Series: Christopher Kontos, MD, New Insights into Skeletal Muscle-Endothelial Cell Interactions in Peripheral Artery Disease

Speaker: Christopher Kontos, MD. Associate Professor of Medicine, Duke University
Topic: “New Insights into Skeletal Muscle-Endothelial Cell Interactions in Peripheral Artery Disease”

Presentation Preview: Peripheral artery disease (PAD) is caused by atherosclerotic obstruction of the peripheral arteries, most commonly the legs. The clinical manifestations of PAD include intermittent claudication, characterized by pain with exertion that is relieved by rest, and critical limb ischemia (CLI), in which patients experience rest pain with or without tissue necrosis and gangrene. Traditionally, these different clinical presentations were thought to be due to differences in the severity of atherosclerotic vascular disease and subsequent differences in limb blood flow. However, individuals with the same degree of vascular disease can present with vastly different phenotypes, suggesting that genetics contribute to the different manifestations of PAD. Recent insights from our group have demonstrated that the response of skeletal muscle cells to ischemia, independent of vascular growth or tissue perfusion, plays an important role in determining outcomes after limb ischemia. In a mouse model of limb ischemia, a polymorphism in BAG3 (Bcl2-associated athanogene-3) was found to play a key role in determining tissue survival vs. loss after limb ischemia, and its potential mechanisms of action and role as a therapeutic target in PAD will be discussed. In addition, several receptors expressed primarily on endothelial cells have been found play a role in modulating skeletal muscle cellular responses to injury, and these receptors’ potential roles in the response to PAD and skeletal muscle differentiation will be discussed.