Journal article
Interference with PPARγ Signaling Causes Cerebral Vascular Dysfunction, Hypertrophy, and Remodeling
Hypertension (Dallas, Tex. 1979), Vol.51(4), pp.867-871
04/2008
DOI: 10.1161/HYPERTENSIONAHA.107.103648
PMCID: PMC2408877
PMID: 18285614
Abstract
The transcription factor PPARγ is expressed in endothelium and vascular muscle where it may exert anti-inflammatory and anti-oxidant effects. We tested the hypothesis that PPARγ plays a protective role in the vasculature by examining vascular structure and function in heterozygous knockin mice expressing the P465L dominant negative mutation in PPARγ (L/+). In L/+ aorta, responses to the endothelium-dependent agonist acetylcholine (ACh) were not affected, but there was an increase in contraction to serotonin, PGF
2α
, and endothelin-1. In cerebral blood vessels both in vitro and in vivo, ACh produced dilation that was markedly impaired in L/+ mice. Superoxide levels were elevated in cerebral arterioles from L/+ mice and responses to ACh were restored to normal with a scavenger of superoxide. Diameter of maximally dilated cerebral arterioles was less, whereas, wall thickness and cross-sectional area was greater in L/+ mice, indicating cerebral arterioles underwent hypertrophy and remodeling. Thus, interference with PPARγ signaling produces endothelial dysfunction via a mechanism involving oxidative stress and causes vascular hypertrophy and inward remodeling. These findings indicate that PPARγ has vascular effects which are particularly profound in the cerebral circulation and provide genetic evidence that PPARγ plays a critical role in protecting blood vessels.
Details
- Title: Subtitle
- Interference with PPARγ Signaling Causes Cerebral Vascular Dysfunction, Hypertrophy, and Remodeling
- Creators
- Andreas M Beyer - Genetics Graduate Program, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USAGary L Baumbach - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USACarmen M Halabi - Genetics Graduate Program, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USAMary L Modrick - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USACynthia M Lynch - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USAThomas D Gerhold - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USAShams M Ghoneim - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USAWillem J de Lange - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USAHenry L Keen - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USAYau-Sheng Tsai - Department of Pathology, University of North Carolina, Chapel Hill, NC, USANobuyo Maeda - Department of Pathology, University of North Carolina, Chapel Hill, NC, USACurt D Sigmund - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USAFrank M Faraci - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.51(4), pp.867-871
- DOI
- 10.1161/HYPERTENSIONAHA.107.103648
- PMID
- 18285614
- PMCID
- PMC2408877
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 04/2008
- 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
- 9984040245302771
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