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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1750.)
© 2004 American Heart Association, Inc.

Brief Reviews

Hepatic Lipase, Lipoprotein Metabolism, and Atherogenesis

Silvia Santamarina-Fojo; Herminia González-Navarro; Lita Freeman; Elke Wagner; Zengxuan Nong

From the Molecular Disease Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Md.

Correspondence to Silvia Santamarina-Fojo, NHLBI, NIH, 10 Center Dr, Bethesda, MD 20892. E-mail silvia{at}mdb.nhlbi.nih.gov

The role of hepatic lipase as a multifunctional protein that modulates lipoprotein metabolism and atherosclerosis has been extensively documented over the last decade. Hepatic lipase functions as a lipolytic enzyme that hydrolyzes triglycerides and phospholipids present in circulating plasma lipoproteins. Hepatic lipase also serves as a ligand that facilitates lipoprotein uptake by cell surface receptors and proteoglycans, thereby directly affecting cellular lipid delivery. Recently, another process by which hepatic lipase modulates atherogenic risk has been identified. Bone marrow transplantation studies demonstrate that hepatic lipase present in aortic lesions markedly alters aortic lesion formation even in the absence of changes in plasma lipids. These multiple functions of hepatic lipase, which facilitate not only plasma lipid metabolism but also cellular lipid uptake, can be anticipated to have a major and complex impact on atherogenesis. Consistently, human and animal studies support proatherogenic and antiatherogenic roles for hepatic lipase. The concept of hepatic lipase as mainly a lipolytic enzyme that reduces atherogenic risk has evolved into that of a complex protein with multiple functions that, depending on genetic background and sites of expression, can have a variable effect on atherosclerosis.

Hepatic lipase is a multifunctional protein that modulates lipoprotein metabolism and atherosclerosis. Hepatic lipase functions as a lipase and as a ligand that facilitates lipoprotein uptake by cell surface receptors and proteoglycans. These multiple functions have a major and complex impact on atherogenesis.

Key Words: transgenic mouse models • lipolytic enzyme • ligand-binding function • macrophages • bone marrow transplantation • aortic atherosclerosis

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