Independent Risk Factor for Moderate to Severe Internal Carotid Artery Stenosis: T786C Mutation of the Endothelial Nitric Oxide Synthase Gene (Molecular Diagnostics and Genetics‪)‬

Atherosclerosis is responsible for one-half of the deaths in Western countries (1). Its pathogenesis, however, remains unclear. The known atherosclerosis risk factors, i.e., increased cholesterol, diabetes mellitus, hypertension, and smoking, are related to vascular dysfunction with underlying monocyte adhesion and invasion, smooth muscle proliferation and migration, platelet activation, and extracellular matrix formation. In both animal and human models, the endothelial NO pathway appears to be involved in atherosclerosis (2). Endothelium-derived NO is synthesized from t-arginine by endothelial nitric oxide Synthase (eNOS) [3] (3), which is encoded by the NOS3 gene on chromosome 7 (4). eNOS is present in the vascular endothelium, platelets, and several other cell types that continuously produce modest amounts of NO (5). NO relaxes vascular smooth muscle, inhibits platelet activation, and modulates migration and growth of vascular smooth muscle cells (6). Indirect evidence suggests that alterations in the NO pathway might be involved in endothelial dysfunction and atherosclerosis (7-9).