Apolipoprotein C-III: a potent modulator of hypertriglyceridemia and cardiovascular disease.

Abstract

PURPOSE OF REVIEW:

The purpose of this article is to summarize the recent epidemiological, basic science, and pharmaceutical research linking apolipoprotein C-III (apoC-III) with the development and treatment of cardiovascular disease (CVD).

RECENT FINDINGS:

ApoC-III is an important emerging target linking hypertriglyceridemia with CVD. ApoC-III is a potent modulator of many established CVD risk factors, and is found on chylomicrons, very-low density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles. Recent studies show that in humans, apoC-III levels are an independent risk factor for CVD, and its presence on lipoproteins may promote their atherogenicity. This year, two large-scale epidemiological studies have linked mutations in apoC-III with increased incidence of CVD and hypertriglyceridemia. ApoC-III raises plasma triglycerides through inhibition of lipoprotein lipase, stimulation of very-low density lipoprotein secretion, and is a novel factor in modulating intestinal triglyceride trafficking. ApoC-III also stimulates inflammatory processes in the vasculature and the pancreas. The combination of raising plasma triglycerides and independently stimulating inflammatory processes makes apoC-III a valuable target for reducing the residual CVD risk in patients already on statin therapy, or for whom triglycerides are poorly controlled. Clinical trials on apoC-III antisense oligonucleotides are in progress.

SUMMARY:

ApoC-III is a potent direct modulator of established CVD risk factors: plasma triglycerides and inflammation. Recent findings show that changes in apoC-III levels are directly associated with changes in cardiovascular risk and the atherogenicity of the lipoproteins on which apoC-III resides. Emerging roles of apoC-III include a role in directing the atherogenicity of high-density lipoprotein, intestinal dietary triglyceride trafficking, and modulating pancreatic β-cell survival. The combination of these roles makes apoC-III an important therapeutic target for the management and prevention of CVD.

• Authors: Alison B Kohan
• Journal: Current opinion in endocrinology, diabetes, and obesity (Curr Opin Endocrinol Diabetes Obes) Vol. 22 Issue 2 Pg. 119-25 (Apr 2015) ISSN: 1752-2978 [Electronic] England
• PMID: 25692924 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Apolipoprotein C-III
• Biomarkers
• Hypolipidemic Agents
• Inflammation Mediators
• Triglycerides

Topics

• Animals
• Apolipoprotein C-III (blood)
• Biomarkers (blood)
• Cardiovascular Diseases (blood, epidemiology, prevention & control)
• Humans
• Hypertriglyceridemia (blood, drug therapy, epidemiology)
• Hypolipidemic Agents (therapeutic use)
• Inflammation Mediators (blood)
• Risk Factors
• Signal Transduction
• Triglycerides (blood)