Smoking and atherosclerotic cardiovascular disease: Part I: Atherosclerotic disease process

Abstract

The normal endothelium inhibits platelet and leukocyte adhesion to the vascular surface maintaining a balance of profibrinolytic and prothrombotic activity. Endothelial function is assessed largely as endothelium-dependent vasomotion, partly based on the assumption that impaired endothelium-dependent vasodilation reflects the alteration of important endothelial functions. Atherosclerotic risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking, are associated with endothelial dysfunction. In the diseased endothelium, the balance between pro- and antithrombotic, pro- and anti-inflammatory, pro- and antiadhesive or pro- and antioxidant effects shifts towards a proinflammatory, prothrombotic, pro-oxidative and proadhesive phenotype of the endothelium. A common mechanism underlying endothelial dysfunction is related to the increased vascular production of reactive oxygen species. Recent studies suggest that inflammation per se, and C-reactive protein in particular, may contribute directly to endothelial dysfunction. The loss of endothelial integrity is a hallmark of atherosclerosis and the causal possible link between each individual risk factor, the development of atherosclerosis and the subsequent clinical events, such as myocardial infarction or stroke.