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Updates on apolipoprotein CIII: fulfilling promise as a therapeutic target for hypertriglyceridemia and cardiovascular disease

Zheng, Chunyu

doi: 10.1097/MOL.0000000000000040
NUTRITION AND METABOLISM: Edited by Frank M. Sacks and Lawrence J. Appel

Purpose of review: The lipid hypothesis of atherosclerosis is mainly predicated on the function of apolipoprotein (apo)B lipoproteins, which promote atherosclerosis, and apoA lipoproteins, which prevent it. However, accumulating evidence suggests causal roles of other apolipoproteins, abundant surface components of apoB and apoA lipoprotein, in promoting atherosclerosis and other metabolic diseases. This article reviews recent literature on one such apolipoprotein: apoCIII.

Recent findings: Population studies have consistently demonstrated that plasma apoCIII strongly predicts cardiovascular disease. ApoCIII's atherogenicity was traditionally attributed to hypertriglyceridemia because of its inhibition on the lipolysis of triglyceride-rich lipoproteins. Recent evidence expands this function and reveals apoCIII's key role in hepatic assembly and secretion of triglyceride-rich lipoproteins. In addition to these indirect atherogenic functions mediated through dyslipidemia, recent research discovers that apoCIII directly provoke proinflammatory responses in vascular cells, including monocytes and endothelial cells. These direct atherogenic effects are dependent on apoCIII. ApoCIII is also involved in pancreatic beta-cell biology and contributes to type I diabetes.

Summary: Recent data further strengthen the theory that apoCIII exerts strong atherogenic functions through both indirect and direct mechanisms. Encouraging results from early stage clinical trials demonstrate that modulating apoCIII per se is a novel and potent therapeutic approach to managing dyslipidemia and cardiovascular disease risk.

Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Correspondence to Chunyu Zheng, ScD, Center for Excellence in Vascular Biology, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, NRB741, Boston MA 02115, USA. Tel: +1 617 525 4387; e-mail: czheng@post.harvard.edu

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins