Coronary vascular function plays a pivotal role in the development, progression,and clinical manifestations of coronary artery disease. One defining characteristic of non-diseased vascular tissue is endothelial release of nitric oxide, which among others inhibits platelet aggregation, attenuates inflammation, decreases cellular proliferation and induces local vascular smooth muscle vasodilation. Despite the central role of dynamic, local vascular function in the cascade causing coronary atherosclerosis and its life-threatening consequences, there are no non-invasive means to assess local coronary endothelial function and hence our understanding of the process and our current clinical approaches are severely and fundamentally limited.
The plan is to address an issue of fundamental importance and clinical relevance. The development, progression, and severity of coronary atherosclerosis are regionally heterogeneous despite the exposure of the entire coronary vasculature to identical genetic and systemic risk factors. The reasons for regional atherosclerotic heterogeneity are incompletely understood but have clinical consequences for millions of people worldwide. We therefore propose to test the hypothesis that local coronary endothelial dysfunction predicts the local progression of coronary atherosclerosis and contributes to local plaque instability and events. In collaboration with Robert G. Weiss and Allison Hays, Johns Hopkins University School of Medicine.