Atherosclerosis Understanding Pathogenesis & Challenge for Treatment PDF

Atherosclerosis is a chronic inflammatory disease that affects medium and large-sized arteries. It begins after birth and the progression depends on several factors – traditional triad: hypertension, hyperlipidemia and diabetes mellitus, then age, sex, smoking and sedentary life-style. At the beginning atherosclerosis is asymptomatic and we cannot estimate appropriately its frequency, but its complications – coronary artery diseases, cerebrovascular diseases, peripheral arterial diseases, which occur late, are responsible for more than half of the yearly mortality in the world. Unfortunately, sudden cardiac death may be the first clinical manifestation. The incipient event is endothelial dysfunction, as a result of injury, caused by high level of cholesterol [especially low-density-lipoprotein LDL], hyperglycemia, hypertension, smoking, infectious agents, and toxins.

Endothelial cells overexpress adhesion molecules – vascular cell adhesion molecule–1 [VCAM-1] and increases recruitment of inflammatory cells– monocytes [Mo], Tcells and subsequent release of monocyte chemo–attractant protein–1 [MCP-1] that results in additional leucocytes recruitment. Injured endothelium allows migration of inflammatory cells that release cytokines and lipids into the intima. That leads to cytokine-mediated progression of atherosclerosis and oxidation of LDL. Macrophages [MP] take up oxi-LDL and form foam-cell. They have metabolic activity and produce cytokines, proliferation of smooth muscle cells and formulate athero-fibrose plaque. Atherosclerotic plaque is composed of superficial layer – fibrose cap and lipid core, that consists of foam cells, extracellular lipid and necrotic cellular debris. It progresses as a result of accumulation of lipid and proliferation of smooth muscle cells and results in luminal narrowing of the arteries which leads to compromised blood and oxygen supply to the tissues. The gradually growing atherosclerotic plaques have thick