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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:619.)
© 2004 American Heart Association, Inc.

Editorials

Regulation of Endothelial Nitric Oxide Synthase by PPAR Agonists: Molecular and Clinical Perspectives

Gerald F. Watts; Bart Staels

From the Lipoprotein Research Unit, Western Australian Institute for Medical Research (G.F.W.), School of Medicine and Pharmacology, University of Western Australia, Perth; and the Département d’Athérosclérose, Institut Pasteur de Lille (B.S.), Institut National de la Santé et de la Recherche Medicale UR545 et Université de Lille 2, Faculté de Pharmacie, Lille, France.

Correspondence to Professor Gerald F. Watts, DSc PhD MD FRCP, Lipoprotein Research Unit, Western Australian Institute for Medical Research, School of Medicine and Pharmacology, University of Western Australia, GPO Box X2213, Perth WA 6847. E-mail gfwatts@cyllene.uwa.edu.au

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

Endothelial nitric oxide synthase (eNOS) is one of three NOS isoforms that catalyze the formation of nitric oxide (NO) and L-citrulline by the oxidation of the guanido-nitrogen group of L-arginine. The cardiovascular importance of this reaction relies on the formation of NO, a signaling molecule that regulates vascular tone, platelet aggregation, oxidative stress, leukocyte adherence, and smooth muscle cell mitogenesis.¹ Peroxisome proliferator-activated receptors (PPARs) are a subfamily of the nuclear receptor family of transcription factors that control the expression of key genes involved in the regulation of metabolism, inflammation, and thrombosis.² Transcriptional control involves ligand activation followed by either heterodimerization with a retinoid X receptor and binding to the promoter region of target genes, or a DNA-binding independent mechanism that interferes negatively with proinflammatory factor pathways. Of the three PPAR isoforms (, ß/, and ), PPAR- is expressed chiefly in fatty acid-oxidizing tissues including liver, skeletal muscle, and heart, but also in endothelial and vascular smooth muscle cells and macrophages within the arterial wall. Despite a plethora of basic research demonstrating that PPAR- activation by synthetic ligands (eg, fibrates) has favorable antiatherogenic properties,² the corresponding effects on eNOS and the biology of NO has surprisingly not yet been explored.

See page 658

In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Goya et al³ demonstrate for the first time that specific PPAR- agonists, such as fenofibrate, regulate eNOS in cultured endothelial cells. Using classical molecular biology techniques and bovine aortic endothelial cells as a model, fenofibrate was . . . [Full Text of this Article]