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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1097.)
© 2005 American Heart Association, Inc.

Editorials

ApoA-V

The Regulation of a Regulator of Plasma Triglycerides

Sven-Olof Olofsson

From the Wallenberg Laboratory, University of Göteborg, Sahlgrenska University Hospital, Göteborg, Sweden.

Correspondence to Sven-Olof Olofsson, Wallenberg Laboratory, University of Göteborg, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. E-mail Sven-Olof.Olofsson@wlab.gu.se

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Apolipoprotein A-V was identified as an open reading frame, approximately 30 kb downstream of the A-I–C-III–A-IV gene cluster, that coded for a 343-aa-long protein with a molecular mass of 39 kDa.¹ Structural analyses have indicated that apoA-V has a multi-domain organization and is relatively hydrophobic/amphipatic.²

See page 1186

ApoA-V is involved in the regulation of plasma triglyceride levels. Thus, human apoA-V transgenic mice have lower triglyceride levels than controls, whereas the knockouts have increased levels.¹ Because hypertriglyceridemia is an independent risk factor for the development of atherosclerosis and cardiovascular diseases, elucidation of the mechanism behind the regulation of apoA-V is of great importance.

Expression of apoA-V is increased by interaction of the heterodimer PPAR (peroxisome proliferator-activator receptor)/RXR (retinoid X receptor) with a "Direct Repeat"1 (DR1) sequence in the apoA-V promoter.^3,4 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Genoux et al⁵ show that the retinoid-related orphan receptors alpha (ROR) 1 and 4 are also involved in the regulation of the apoA-V gene by interaction with the DR1 binding site. This interaction occurs with the human gene but not in mice, which is logical because the motive is not conserved in mice.

ROR has been crystallized with cholesterol in the binding site.⁶ Also, cholesterol stabilizes ROR, and depletion of cellular cholesterol by statins has been shown to modulate the transcriptional activity of ROR.⁶ For a review, see Boukhtouche et al.⁷ However, it remains to be clarified whether cholesterol is a physiological ligand for ROR.

The . . . [Full Text of this Article]

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