Endothelial Dysfunction: Clinical Implications in Cardiovascular Disease and Therapeutic Approaches

Atherosclerosis is a chronic progressive vascular disease. It starts early in life, has a long asymptomatic phase, and a progression accelerated by various cardiovascular risk factors. The endothelium is an active inner layer of the blood vessel. It generates many factors that regulate vascular tone, the adhesion of circulating blood cells, smooth muscle proliferation, and inflammation, which are the key mechanisms of atherosclerosis and can contribute to the development of cardiovascular events. There is growing evidence that functional impairment of the endothelium is one of the first recognizable signs of development of atherosclerosis and is present long before the occurrence of atherosclerotic cardiovascular disease. Therefore, understanding the endothelium's central role provides not only insights into pathophysiology, but also a possible clinical opportunity to detect early disease, stratify cardiovascular risk, and assess response to treatments. In the present review, we will discuss the clinical implications of endothelial function as well as the therapeutic issues for endothelial dysfunction in cardiovascular disease as primary and secondary endothelial therapy. GRAPHICAL ABSTRACT: [Image: see text]