Abstract
Impaired vascular function in transgenic mice with smooth muscle cell specific dominant negative hPPARγ expression
The FASEB journal, Vol.21(6), pp.A861-A861
2007
DOI: 10.1096/fasebj.21.6.A861-b
Abstract
PPARγ is a ligand activated transcription factor. Dominant negative (DN) mutations in PPARγ have been reported in patients with type 2 diabetes and early onset hypertension. To explore the role of PPARγ in vascular smooth muscle cells (vSMC) in vivo, we generated transgenic (Tg) mice designed to interfere with PPARγ‐dependent signaling by specifically targeting expression of a DN PPARγ (P467L) to SMC. Transgene expression in tissues containing SMC, including aorta was confirmed by RNase protection. Vascular function in aorta from Tg mice and non‐Tg (NT) littermates was examined in vitro. Remarkably, aorta of Tg animals exhibited endothelial dysfunction and an impaired response to nitric oxide as evidenced by significantly lower relaxation to acetylcholine (ACh 10μM, 9±2%) and sodium nitroprusside (SNP 10μM, 44±4%) than aorta of NT (38±3% for ACh, 86±1% for SNP, P<0.001). Submaximal relaxation to the endothelial‐independent vasodilator paperverine was slightly but significantly impaired. We are currently testing if the impaired response to NO is due to impaired cGMP‐dependent signaling. Interestingly, aorta of Tg mice also contracted considerably more to endothelin‐1 (ET‐1 0.1 μM, 302±29 mg) than did aorta of NT (44±6 mg, P<0.001). This increase in contraction was inhibited by the ET‐A receptor antagonist BQ‐123. These data suggest that vSMC PPARγ plays a pivotal role in the regulation of vascular tone.
Details
- Title: Subtitle
- Impaired vascular function in transgenic mice with smooth muscle cell specific dominant negative hPPARγ expression
- Creators
- Carmen M. Halabi - MSTP and Genetics Graduate ProgramAndreas M. BeyerHenry L. Keen - University of IowaWillem J. De Lange - University of IowaFrank M. Faraci - University of IowaCurt D. Sigmund - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.21(6), pp.A861-A861
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.21.6.A861-b
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 2007
- Academic Unit
- Molecular Physiology and Biophysics; Neuroscience and Pharmacology; Internal Medicine; Cardiovascular Medicine; Iowa Institute of Human Genetics
- Record Identifier
- 9984304741502771
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