Apolipoproteins, Reverse Cholesterol Transport and Coronary Heart Disease
Several epidemiological and clinical studies revealed an inverse correlation between low plasma concentrations of high-density lipoprotein (HDL) cholesterol as well as its major protein component apolipoprotein A-I (apo A-I) and the risk of myocardial infarction (reviewed in Gordon and Rifkind 1989). Family and twin studies suggested partial heredity of low HDL cholesterol levels and have put the influence of genes at 35%-50% (Hunt et al. 1989; Assmann et al. 1989a). Frequently, familial HDL cholesterol deficiency was paralleled with a family history of premature coronary heart disease (CHD) (Pometta et al. 1979; DeBacker et al. 1986). Thus, a causal role between low levels of HDL cholesterol and coronary risk appears well established. However, the pathophysiological relationship between decreased serum concentrations of HDL cholesterol and the development of coronary heart disease has still remained obscure. The reverse cholesterol transport model (Glomset 1968) is most widely used to explain the role of HDL in lipid metabolism and in atherogenesis. HDL precursors, so-called nascent HDL or HDL disks, are generated through lipolysis of chylomicrons and VLDL as well as by direct secretion of the liver (reivewed in Brunzell 1989 and Assmann et al. 1989b). HDL subclasses and reconstituted HDL-like particles that contain apo A-I were shown to take up excess cellular cholesterol by interaction with specific cell surface recognition sites (reviewed in Assmann et al. 1989b). Upon esterification of free cholesterol by lecithin:cholesterol acyltransferase (LCAT), the core of small and dense HDL particles becomes enriched in cholesterol esters and their particle size increases (reviewed in Norum et al. 1989).
KeywordsCholesterol Codon Lipase Cysteine Anemia
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