HDL metabolism in hypertriglyceridemic states: an overview

Reduced plasma high-density lipoprotein (HDL) cholesterol levels have been recognized as a highly significant independent risk factor for atherosclerotic cardiovascular disease. HDL levels are also inversely related to plasma triglyceride levels and there is a dynamic interaction between HDL and triglyceride (TG) rich lipoproteins in vivo. The mechanisms underlying the lowering of HDL in hypertriglyceridemic states have not been fully elucidated, but there is evidence to suggest that triglyceride enrichment of HDL, a common metabolic consequence of hypertriglyceridemia, may play an important role in this process. There is accumulating evidence to suggest that the primary mechanisms leading to reduced plasma HDL cholesterol levels and HDL particle number in hypertriglyceridemic states may be due to any one or a combination of the following possibilities: (1) small HDL particles, which are the product of the intravascular lipolysis of triglyceride-enriched HDL, may be cleared more rapidly from the circulation, (2) triglyceride-enriched HDL may be intrinsically more unstable in the circulation, with apo A-I loosely bound, (3) the lipolytic process itself of triglyceride-enriched HDL may lower HDL particle number by causing apo A-I to be shed from the HDL particles and cleared from the circulation, (4) a dysfunctional lipoprotein lipase or reduced LPL activity may contribute to the lowering of HDL levels by reducing the availability of surface constituents of triglyceride-rich lipoproteins that are necessary for the formation of nascent HDL particles. This review summarizes the evidence that triglyceride-enrichment of HDL is an important factor determining the rate at which HDL is catabolized, a mechanism which could explain, at least in part, the reduced plasma HDL cholesterol levels and particle number frequently observed in hypertriglyceridemic states.