The metabolism of high-density lipoproteins

Although high-density lipoproteins (HDLs) have been shown to be the best single indicator of the risk of coronary heart disease (CHD), relatively little is known about their metabolism. Accordingly, only limited strategies are available for therapeutically raising plasma HDL levels. The circulating HDL particle is assembled in the blood as the result of remodeling the nascent discoidal HDL followed by transfer of lipid and protein components from other lipoproteins. The catabolism of HDL is equally complex. The receptor-mediated removal mechanism of HDL from the plasma has yet to be substantiated. Despite the extensive studies performed, no clear mechanism has emerged whereby HDL particles protect the arteries from atherosclerosis. Reverse cholesterol transport remains an attractive hypothesis, but several other potential mechanisms may also play a role in the interaction between HDL and the arterial surface. Recent studies related to the regulation of HDL metabolism are discussed with particular emphasis on the potential role of the postprandial state. A brief discussion is also provided on potential future strategies for regulating HDL levels through pharmacologic intervention.