Published online before print September 4, 2007, doi: 10.1161/HYPERTENSIONAHA.107.097519
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(Hypertension. 2007;50:844.)
© 2007 American Heart Association, Inc.
Editorial Commentaries |
Is Peroxisome Proliferator-Activated Receptor-
a New "Pal" of Renin?
From the Department of Molecular Physiology and Biophysics (E.T.W., C.D.S.), Molecular Biology Graduate Program (H.I.), and Department of Internal Medicine (H.L.K., C.D.S.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City.
Correspondence to Curt D. Sigmund, Departments of Internal Medicine and Physiology and Biophysics, 3181B Medical Education and Biomedical Research Facility, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242. E-mail curt-sigmund@uiowa.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that have a growing list of pleiotropic effects and have been implicated in inflammation, Alzheimer’s disease, cancer, diabetes, obesity, and cardiovascular diseases, including atherosclerosis and hypertension. The 
-subtype of the receptor (PPAR) has been shown to regulate transcription of target genes by binding as a heterodimer with retinoid X receptor (RXR) to a hexameric direct repeat called the PPAR response element (PPRE). The consensus sequence of the PPRE is AGGTCANAGGTCA, where N is a single nucleotide separating the 2 receptor-binding half sites (italicized). For classic PPAR response genes, PPAR/RXR
heterodimers sit on the PPRE and recruit corepressors in the absence of ligand. On ligand binding, a conformational change in PPAR is induced, resulting in a replacement of the corepressors with coactivators, thus achieving ligand-activated transcription of the target gene.
Thiazolidinediones (TZDs) are high-affinity synthetic ligands of PPAR used clinically to improve insulin sensitivity in type-2 diabetes. Reports that TZDs also have cardioprotective effects, such as reducing blood pressure, suggest a potential link between PPAR activity and the cardiovascular system. Compelling genetic evidence supporting this includes reports showing that patients with dominant-negative mutations in PPAR exhibit severe early onset hypertension.1 These data also indirectly suggest that the beneficial effects of TZDs on blood pressure may not be derived solely from improved glycemic controls but perhaps also from direct effects of PPAR in cardiovascular tissues, such as the blood vessel. Consequently, understanding the fundamental mechanisms controlling blood pressure by
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Is Involved in the Control of Renin Gene Expression
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