Potential target sites to modulate vascular endothelial dysfunction: Current perspectives and future directions

Endothelium is innermost lining of the blood vessel and it regulates the vascular tone. It plays a critical role in the mechanics of blood flow, regulation of coagulation, leukocyte adhesion, vascular smooth muscle cell (VSMC) growth and immune function. Endothelial dysfunction results in reduced vasodilatation, proinflammatory state and prothrombotic properties. Various experimental evidences revealed that reduced nitric oxide production and increased oxidative stress lead to vascular endothelial dysfunction (VED). Environmental factors such as cigarette smoking, alcohol consumption and exposure to arsenic play a critical role in the development of endothelial dysfunction. Vascular endothelial dysfunction is a hallmark for various cardiovascular disorders such as hypertension, atherosclerosis, heart failure, myocardial infarction and stroke. However, the pathological mechanism involved in the vascular endothelial dysfunction is poorly understood. The present review delineates various potential target sites for vascular endothelial dysfunction, which may open a new vista for exploring novel pharmacological agents to treat various cardiovascular disorders. (C) 2007 Elsevier Ireland Ltd. All rights reserved.