Cardiovascular diseases remain the principal cause of morbidity and mortality in the Westernized world. Atherosclerosis is the common pathophysiological process underlying ischemic heart disease, cerebrovascular accidents and peripheral vascular disease. Understanding of the pathogenesis of atherosclerosis has tremendously increased in the last decade. For years, atherosclerosis had been considered as a degenerative process of the arteries. Nowadays, atherosclerosis is seen as an inflammatory disease of the artery resulting from chronic endothelial injury. Platelets have proinflammatory and growthregulatory properties that may contribute to the progression and destabilization of atherosclerotic plaques. Platelets activate endothelium, promote lipoprotein and lipid peroxidation, mediate leukocyte–endothelial interaction and stimulate smooth muscle cell proliferation. An acute clinical syndrome usually involves thrombosis triggered by the rupture of a vulnerable atherosclerotic plaque. Incorporation of mural platelet-rich thrombi at the site of an unstable plaque contributes to the progression of atherosclerotic lesions.

Pathogenesis of atherosclerosis

Response to injury

Healthy endothelium maintains vascular integrity. It provides a non-thrombogenic inner layer of the vessel wall, and tends to dilate the vessel by releasing endotheliumderived relaxing factor (nitric oxide, NO), endotheliumderived hyperpolarizing factor (EDHF) and prostacylin (PGI2). NO and PGI2 both inhibit the adhesion and aggregation of platelets. Furthermore, healthy endothelium has fibrinolytic properties and impedes leukocyte adhesion.

Chronic endothelial injury is a key feature in the pathogenesis of atherosclerosis. Cardiovascular risk factors such as dyslipidemia, hypertension, smoking, diabetes, hyperhomocysteinemia and systemic infection or inflammation result in increased oxidative stress of the vascular wall, endothelial dysfunction and platelet hyperactivity (Fig. 48.1).