Targeting ApoC-III to Reduce Coronary Disease Risk

Abstract

Triglyceride-rich lipoproteins (TRLs) are causal contributors to the risk of developing coronary artery disease (CAD). Apolipoprotein C-III (apoC-III) is a component of TRLs that elevates plasma triglycerides (TGs) through delaying the lipolysis of TGs and the catabolism of TRL remnants. Recent human genetics approaches have shown that heterozygous loss-of-function mutations in APOC3, the gene encoding apoC-III, lower plasma TGs and protect from CAD. This observation has spawned new interest in therapeutic efforts to target apoC-III. Here, we briefly review both currently available as well as developing therapies for reducing apoC-III levels and function to lower TGs and cardiovascular risk. These therapies include existing options including statins, fibrates, thiazolidinediones, omega-3-fatty acids, and niacin, as well as an antisense oligonucleotide targeting APOC3 currently in clinical development. We review the mechanisms of action by which these drugs reduce apoC-III and the current understanding of how reduction in apoC-III may impact CAD risk.

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Correspondence to Daniel J. Rader.

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Sumeet A. Khetarpal, Arman Qamar, John S. Millar, and Daniel J. Rader declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Nonstatin Drugs

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Khetarpal, S.A., Qamar, A., Millar, J.S. et al. Targeting ApoC-III to Reduce Coronary Disease Risk. Curr Atheroscler Rep 18, 54 (2016). https://doi.org/10.1007/s11883-016-0609-y

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Keywords

  • Triglycerides
  • Triglyceride-rich lipoproteins
  • CAD
  • apoC-III
  • PPAR
  • Statin
  • Niacin