%0 Journal Article
%T Hyperglycemia and Endothelial Dysfunction in Atherosclerosis: Lessons from Type 1 Diabetes
%A Steven Daniel Funk
%A Arif Yurdagul Jr
%A A. Wayne Orr
%J International Journal of Vascular Medicine
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/569654
%X A clear relationship between diabetes and cardiovascular disease has been established for decades. Despite this, the mechanisms by which diabetes contributes to plaque formation remain in question. Some of this confusion derives from studies in type 2 diabetics where multiple components of metabolic syndrome show proatherosclerotic effects independent of underlying diabetes. However, the hyperglycemia that defines the diabetic condition independently affects atherogenesis in cell culture systems, animal models, and human patients. Endothelial cell biology plays a central role in atherosclerotic plaque formation regulating vessel permeability, inflammation, and thrombosis. The current paper highlights the mechanisms by which hyperglycemia affects endothelial cell biology to promote plaque formation. 1. Cardiovascular Disease and Diabetes Mellitus Treatment of cardiovascular disease (CVD), manifesting in the form of myocardial infarction, stroke, and peripheral artery disease, represents one of biomedical sciences best success stories over the past several decades [1, 2]. Through clinical trials, epidemiology, and basic science, we have identified a host of risk factors and designed drugs targeting these risk factors that improve patient survival. The cholesterol-lowering statin family of therapeutics reduces the 5-year risk of cardiovascular-associated mortality by ~25% in patients with a history of prior CVD [3]. However, statins have not shown similar protection in patients without a prior history of CVD [4, 5], and CVD remains the leading cause of death in developed countries [2, 6]. Furthermore, the current obesity epidemic threatens to worsen the incidence of CVD in the coming years, undoing the progress we have made to this point [7]. More than 80% of the CVD-associated death and disability is attributed to atherosclerosis, the excessive accumulation of lipids, cholesterol, inflammatory cells, and connective tissue in the vessel wall [8, 9]. While clinically silent for decades, atherosclerotic plaques can grow to occlude the vessel lumen reducing blood flow to target tissues [8, 9]. Although this form of vessel occlusion can result in significant discomfort (e.g., angina pectoris), clinical events most often result from thrombus formation due to plaque deterioration or rupture resulting in a rapid cessation in blood flow to target tissue. Theories concerning the pathogenesis of atherosclerosis have changed over the years, maturing concomitantly with our understanding of vascular biology. We now know that atherosclerosis is a chronic inflammatory
%U http://www.hindawi.com/journals/ijvm/2012/569654/