Emerging evidence that ApoC-III inhibitors provide novel options to reduce the residual CVD

Taskinen, M.-R., Packard, C. J. and Borén, J. (2019) Emerging evidence that ApoC-III inhibitors provide novel options to reduce the residual CVD. Current Atherosclerosis Reports, 21(8), 27. (doi: 10.1007/s11883-019-0791-9) (PMID:31111320) (PMCID:PMC6527792)

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Purpose of Review: Apolipoprotein C-III (apoC-III) is known to inhibit lipoprotein lipase (LPL) and function as an important regulator of triglyceride metabolism. In addition, apoC-III has also more recently been identified as an important risk factor for cardiovascular disease. This review summarizes the mechanisms by which apoC-III induces hypertriglyceridemia and promotes atherogenesis, as well as the findings from recent clinical trials using novel strategies for lowering apoC-III. Recent Findings: Genetic studies have identified subjects with heterozygote loss-of-function (LOF) mutations in APOC3, the gene coding for apoC-III. Clinical characterization of these individuals shows that the LOF variants associate with a low-risk lipoprotein profile, in particular reduced plasma triglycerides. Recent results also show that complete deficiency of apoC-III is not a lethal mutation and is associated with very rapid lipolysis of plasma triglyceride-rich lipoproteins (TRL). Ongoing trials based on emerging gene-silencing technologies show that intervention markedly lowers apoC-III levels and, consequently, plasma triglyceride. Unexpectedly, the evidence points to apoC-III not only inhibiting LPL activity but also suppressing removal of TRLs by LPL-independent pathways. Summary: Available data clearly show that apoC-III is an important cardiovascular risk factor and that lifelong deficiency of apoC-III is cardioprotective. Novel therapies have been developed, and results from recent clinical trials indicate that effective reduction of plasma triglycerides by inhibition of apoC-III might be a promising strategy in management of severe hypertriglyceridemia and, more generally, a novel approach to CHD prevention in those with elevated plasma triglyceride.

Item Type:Articles
Keywords:ApoC-III, CVD, genetic variants, lipoproteins, remnants, triglycerides.
Glasgow Author(s) Enlighten ID:Packard, Professor Chris
Authors: Taskinen, M.-R., Packard, C. J., and Borén, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Current Atherosclerosis Reports
ISSN (Online):1534-6242
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Current Atherosclerosis Reports 21(8):27
Publisher Policy:Reproduced under a Creative Commons License

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