High-density lipoproteins in the prevention of atherosclerotic heart disease. Part II. Biochemical role in the pathogenesis of atherosclerosis.

Evidence is presented that high-density lipoprotein (HDL) promotes the efflux of cholesterol from cells in vitro, and may thus play an important role in the transport of cholesterol from non-hepatic tissues to the liver for excretion. Hypothetical schemes are presented whereby this may be achieved in vivo. This putative function of HDL may be of particular importance in situations in which the capacity of cells to limit the uptake of cholesterol is exceeded, and may therefore constitute the basis for the proposed antiatherogenic action of plasma HDL. However, direct data on the transport function of HDL in intact organisms are meagre. Furthermore, a characteristic of mature atherosclerotic lesions is the extracellular, rather than the intracellular, deposition of cholesterol and other lipids, and the degree to which HDL may influence this process has not been demonstrated. Finally, in inherited disorders which markedly impair the putative HDL transport pathway, atherosclerotic heart disease is generally not an early or severe complication. Despite these caveats, the physiological significance of HDL deserves further attention in order to clarify the uncertainties enumerated above. The clinical application of plasma HDL assay is limited at present to excluding the clinically non-deleterious condition of hyperalpha (HDL)-lipoproteinaemia in patients suffering from familial hypercholesterolaemia.