High-density lipoprotein turnover

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High-density lipoprotein (HDL) metabolism has been reviewed from information derived from turnover studies in humans. The two major HDL apoproteins AI and AII have different removal rates, reflecting the faster catabolism of HDL 2 than of HDL 3. This is caused by the continual cycle of formation of HDL 2 from HDL 3 and its reversion to HDL 3, in response to the need to transport cholesterol and other lipids from extrahepatic cells and catabolized triglyceride-rich lipoproteins. The conversion of HDL 2 to HDL 3 is mediated through a hepatic lipase. Because this lipase is inhibited by estrogen and stimulated by androgens, women have higher HDL 2 levels than men. The synthesis of apoproteins AI and AII is also higher in women than in men. Nutrition also influences HDL turnover. Carbohydrates increase AI and HDL 2 removal, whereas polyunsaturated fatty acids inhibit synthesis. Vegeterians show high HDL removal rates. Thus low-fat, low-cholesterol diets generally lead to lower HDL levels. Disorders that alter HDL composition (such as alcoholic liver disease or Tangier disease) accelerate HDL removal. Other HDL proteins such as apoproteins C and E show faster turnover rates than AI and AII, since the former exchange with triglyceride-rich lipoproteins and participate in their catabolism. Diminished exchange of apoprotein C from HDL to chylomicrons may be responsible for the diminished catabolism of these particles in type V hyperlipoproteinemia. The unusual turnover characteristics of HDL apoprotein AIV are reviewed, suggesting a dual role for this protein in both triglyceride and cholesterol transport. The striking relationship between very low-density lipoprotein (VLDL) and HDL metabolism is expressed in an inverse association between their respective removal rates. That is, when the VLDL removal rate is slow, as in hypertriglyceridemia, HDL removal is fast. This leads to low HDL levels in hypertriglyceridemia, a combination that is favorable for atherosclerosis. The hypothesis is that in hypertriglyceridemia a high rate of transfer of triglyceride to HDL 3 occurs; this produces triglyceride-rich HDL 2, which is highly susceptible to catabolism by hepatic lipase. This not only depletes the HDL 2 concentration but reduces the capacity of available HDL 3 to participate in reverse cholesterol transport