期刊
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
卷 22, 期 2, 页码 119-125出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MED.0000000000000136
关键词
apolipoprotein C-III; cardiovascular disease; diabetes; intestinal lipid transport; obesity; vascular inflammation
资金
- National Institutes of Health [DK101663]
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 beta-cell survival. The combination of these roles makes apoC-III an important therapeutic target for the management and prevention of CVD.
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