Atherosclerosis is due to
Atherosclerosis is a slowly progressive disease of large to medium-sized muscular aeries and large elastic aeries characterised by elevated focal intimal fibrofattyPlaques. Principal larger vessels affected are the abdominal aoa, descending thoracic aoa, internal carotid aeries and medium to smaller sized vessels affected are popliteal aeries, coronary aeries, and circle of Willis in brain. The atheroma may be preceded by fatty streaks that are intimal collection of lipid-laden macrophages and smooth muscle cells, occurring in persons as young as one year of age.The disease typically manifests in later life as the vessel lumen is compromised, predisposing to thrombosis and the underlying media is thinned, predisposing to aneurysm formation. It is the number one killer disease, 50 per cent of all deaths in the USA are attributed to atherosclerosis and half of theseare due to acute myocardial infarctions. The remainder include cerebrovascular accidents ("stroke"), aneurysm rupture, mesenteric occlusion and gangrene of theextremities. Etiological Factors Major risk factors in CHD have been discussed earlier. Risk of developing atherosclerosis increases with age, a positive family history, cigarette smoking, diabetes mellitus, hypeension, and hypercholesterolemia. The risk is correlated with elevated LDL and inversely related to the HDL level. Hereditary defects, e.g. familial hypercholesterolemia involving the LDL receptor or the LDL apoproteins cause elevated LDL, hypercholesterolemia andaccelerated atherosclerosis. Lesser influences on the risk of atherosclerosis include sedentary, or high-stress lifestyle, obesity and oral contraceptives.Ref: M.N. Chatterjee - Textbook of Biochemistry, 8th edition, page no: 454 - 456
HDL receptor defect
Apo protein E deficiency
Decreased LDL activity
Decreased lipoprotein lipase
Metabolism of lipid