Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis.
Although it has been known for over 50 years that lipoprotein lipase (LPL) hydrolyzes triglyceride in chylomicrons, during the past half decade there has been a reinterest in the physiologic and pathophysiologic actions of this enzyme. In part, this has coincided with clinical studies implicating increased postprandial lipemia as a risk factor for atherosclerosis development. In addition, the recent creation of genetically altered mice with hypertriglyceridemia has focused the interest of geneticists and physiologists on the pathophysiology of triglyceride metabolism. As reviewed in this article, it is apparent that the lipolysis reaction is only partially understood. Several factors other than LPL are critical modulators of this process, in part, because the reaction requires the lipoproteins to interact with the arterial or capillary wall. Among the factors that affect this are the apolipoprotein composition of the particles, the size of the lipoproteins, and how LPL is displayed along the endothelial luminal surface. Zilversmit's observation that LPL activity is found in greater amounts in atherosclerotic than normal arteries has led to a large number of experiments linking LPL with atherogenesis. In medium and large arteries LPL is found on the luminal endothelial surface and in macrophage-rich areas within the plaque. LPL actions in both of these locations probably have major effects on the biology of the blood vessel. Possible atherogenic actions for this LPL based on in vitro experiments are reviewed.
Goldberg
I J
IJ
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032.
D000818:Animals; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D002914:Chylomicrons / Q000378:metabolism; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008066:Lipolysis / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology; D051379:Mice
D002914:Chylomicrons; D008074:Lipoproteins; D008071:Lipoprotein Lipase