doi: 10.1161/01.ATV.0000193889.65915.f9
© 2005 American Heart Association, Inc.
Editorials |
Apolipoprotein AV
Low Concentration, High Impact
From the Departments of General Internal Medicine, Endocrinology and Metabolism (P.C.N.R., K.W.v.D., L.M.H.), Human Genetics (K.W.v.D.), and Cardiology (L.M.H.), Leiden University Medical Center, and TNO-Quality of Life, Department of Biomedical Research (P.C.N.R., L.M.H.), Gaubius Laboratory, Leiden, The Netherlands.
Correspondence to Patrick C.N. Rensen, PhD, Leiden University Medical Center, Department of Endocrinology and Metabolism, C4-R81, Albinusdreef 2, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail P.C.N.Rensen@lumc.nl.
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Hypertriglyceridemia is an independent risk factor for coronary heart disease.1 Apolipoproteins that have been shown to affect plasma triglyceride (TG) levels include apolipoprotein E (apoE) and the C-apolipoproteins (apoCI, apoCII, and apoCIII). The recently identified apoAV is the newest member of this family of apolipoproteins affecting plasma TG levels.2,3 ApoAV is a 39-kDa protein (343 amino acids) that is expressed exclusively by the liver. Plasma TG concentrations in mice were 4-fold increased on deficiency of the endogenous apoa5 gene and were decreased by 65% on expression of the human APOA5 gene.2 Subsequent studies have shown that adenovirus-mediated transfer of murine apoa5 to mice resulted in a dose-dependent reduction of plasma TG.4,5 These studies have thus established an important role of apoAV in TG homeostasis.
See page 2573
Several groups have studied the mechanism underlying the effect of apoAV on TG metabolism. ApoAV has been proposed to affect TG levels by both an intra- and extracellular effect: (1) apoAV may inhibit the hepatic secretion of VLDL,5,6 and (2) apoAV may facilitate the clearance of TG from plasma.5,7,8 Evidence for these two mechanisms has been mainly obtained from mouse models that overexpress apoAV.
In this issue of Atherosclerosis, Thrombosis, and Vascular Biology, Grosskopf et al9 extend these studies on the mechanisms underlying the effects of apoAV on TG metabolism, by using apoAV-deficient (apoa5–/–) mice. From a diverse set of experiments, the elevation of TG in apoa5–/– mice is attributed to the disturbance of two pathways: (1) reduction in lipoprotein
Related Article:
Arterioscler Thromb Vasc Biol 2005 25: 2573-2579.
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