Chapter 16. Atherosclerosis

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This chapter elaborates the pathology and development of drug for atherosclerosis that is an extremely common disease of the large arteries, which constitutes the pathologic basis for most coronary heart disease, stroke, aneurysm and occlusive arterial disease. The studies show that adipose tissue serves as a potentially important site of cholesterol production and as a reservoir of slowly mobilizable cholesterol. Lipid-filled cells, foam cells, are a prominent feature of the atherosclerotic lesion, and contribute to the core of cellular debris, the so-called gruel of advanced lesions. This material can embolize directly from ruptured plaques or serve as a thrombogenic focus. Cholesterol accumulated in atheromatous lesions is largely esterified with fatty acids, especially oleic acid. The change in fatty acid composition of cholesterol esters between circulating lipoproteins and atheromas indicates an esterification process operative in the developing lesion. Enzymes in normal artery catalyze both synthesis and hydrolysis of cholesterol esters. Reaction rates of esterification and hydrolysis are strongly dependent on the physical state of the reactants.

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