Hypoxia up-regulates expression of peroxisome proliferator-activated receptor gamma angiopoietin-related gene (PGAR) in cardiomyocytes: role of hypoxia inducible factor 1alpha.

Abstract	Peroxisome proliferator-activated receptors (PPAR), especially the PPARalpha and PPARgamma, are associated with an extraordinary diverse spectrum of cardiovascular diseases including hypertension, angiogenesis, cardiac hypertrophy, and atherosclerosis. PGAR (for PPAR gamma angiopoietin-related gene) is a recently identified PPAR target gene which is associated with adipose differentiation, systemic lipid metabolism, energy homeostasis, and possibly angiogenesis. We report here that WY-14643, a selective PPARalpha ligand up-regulated PGAR expression in neonatal rat cardiomyocytes. In parallel to activating the expression of vascular endothelial growth factor and glucose transporter-4, hypoxia increased PGAR mRNA levels. PGAR expression was also increased by desferrioxamine and CoCl(2), but not by sodium cyanide, results consistent with the pharmacological features of hypoxia-responsive genes. These studies are the first to demonstrate that hypoxia increases the mRNA levels of a PPAR target gene in cardiomyocytes. Furthermore, infection with adenoviral vectors encoding the wild-type or a hybrid form of HIF-1alpha highly increased PGAR mRNA levels. In contrast, neither hypoxia nor overexpression of HIF-1alpha affected the mRNA levels of PPARalpha, PPAR gamma, and muscle carnitine palmitoyltransferase, a known PPARalpha target gene. These results suggest that hypoxic activation of PGAR expression is likely mediated by HIF-1 but not the PPARalpha/RXR pathway.
Authors	Adam J Belanger, Hsienwie Lu, Taro Date, Louis X Liu, Karen A Vincent, Geoffery Y Akita, Seng H Cheng, Richard J Gregory, Canwen Jiang
Journal	Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 34 Issue 7 Pg. 765-74 (Jul 2002) ISSN: 0022-2828 [Print] England
PMID	12099716 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright 2002 Elsevier Science Ltd. All rights reserved.
Chemical References	ANGPTL2 protein, human Angiogenesis Inducing Agents Angiopoietin-1 Angiopoietin-2 Angiopoietin-Like Protein 2 Angiopoietin-like Proteins Angiopoietins Angpt1 protein, rat Blood Proteins DNA-Binding Proteins Glycoproteins HIF1A protein, human Hif1a protein, rat Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Intercellular Signaling Peptides and Proteins Membrane Glycoproteins Muscle Proteins Nuclear Proteins Transcription Factors
Topics	Angiogenesis Inducing Agents (metabolism) Angiopoietin-1 Angiopoietin-2 Angiopoietin-Like Protein 2 Angiopoietin-like Proteins Angiopoietins Animals Blood Proteins DNA-Binding Proteins (metabolism) Gene Expression Regulation Glycoproteins (metabolism) Humans Hypoxia (metabolism) Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Intercellular Signaling Peptides and Proteins Membrane Glycoproteins (metabolism) Muscle Proteins (metabolism) Myocytes, Cardiac (metabolism) Nuclear Proteins (metabolism) Rats Transcription Factors Up-Regulation

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