title: 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.
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, 11-125 SCTR, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: Sumeet A
authors.initials: SA
authors.lastname: Khetarpal
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, 11-125 SCTR, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: Arman
authors.initials: A
authors.lastname: Qamar
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, 11-125 SCTR, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Millar
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, 11-125 SCTR, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA. rader@mail.med.upenn.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D053305:Apolipoprotein C-III / Q000502:physiology*; D003324:Coronary Artery Disease / Q000209:etiology* / Q000517:prevention & control*; D006801:Humans; D008074:Lipoproteins; D016376:Oligonucleotides, Antisense; D012307:Risk Factors; D014280:Triglycerides
chemical_list: D053305:Apolipoprotein C-III; D008074:Lipoproteins; D016376:Oligonucleotides, Antisense; D014280:Triglycerides; C030087:lipoprotein triglyceride
keywords: CAD; Niacin; PPAR; Statin; Triglyceride-rich lipoproteins; Triglycerides; apoC-III