Interference with PPARγ Function in Smooth Muscle Causes Vascular Dysfunction and Hypertension

Carmen M Halabi; Andreas M Beyer; Willem J de Lange; Henry L Keen; Gary L Baumbach; Frank M Faraci; Curt D Sigmund

doi:10.1016/j.cmet.2007.12.008

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Interference with PPARγ Function in Smooth Muscle Causes Vascular Dysfunction and Hypertension

Journal article

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Interference with PPARγ Function in Smooth Muscle Causes Vascular Dysfunction and Hypertension

Carmen M Halabi, Andreas M Beyer, Willem J de Lange, Henry L Keen, Gary L Baumbach, Frank M Faraci and Curt D Sigmund

Cell metabolism, Vol.7(3), pp.215-226

2008

DOI: 10.1016/j.cmet.2007.12.008

PMCID: PMC2275166

PMID: 18316027

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Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor that plays a critical role in metabolism. Thiazolidinediones, high-affinity PPARγ ligands used clinically to treat type II diabetes, have been reported to lower blood pressure and provide other cardiovascular benefits. Some mutations in PPARγ ( PPARG) cause type II diabetes and severe hypertension. Here we tested the hypothesis that PPARγ in vascular muscle plays a role in the regulation of vascular tone and blood pressure. Transgenic mice expressing dominant-negative mutations in PPARγ under the control of a smooth-muscle-specific promoter exhibit a loss of responsiveness to nitric oxide and striking alterations in contractility in the aorta, hypertrophy and inward remodeling in the cerebral microcirculation, and systolic hypertension. These results identify PPARγ as pivotal in vascular muscle as a regulator of vascular structure, vascular function, and blood pressure, potentially explaining some of the cardioprotective effects of thiazolidinediones.

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Title: Subtitle: Interference with PPARγ Function in Smooth Muscle Causes Vascular Dysfunction and Hypertension
Creators: Carmen M Halabi - Genetics Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Andreas M Beyer - Genetics Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Willem J de Lange - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Henry L Keen - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Gary L Baumbach - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Frank M Faraci - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Curt D Sigmund - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.7(3), pp.215-226
Publisher: Elsevier Inc
DOI: 10.1016/j.cmet.2007.12.008
PMID: 18316027
PMCID: PMC2275166
ISSN: 1550-4131
eISSN: 1932-7420
Language: English
Date published: 2008
Academic Unit: Molecular Physiology and Biophysics; Pathology; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984040555602771

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