Abstract
Interference with Peroxisome Proliferator Activated Receptor Gamma (PPARG) in smooth muscle causes aortic dysfunction via a Rho‐kinase‐dependent mechanism
The FASEB journal, Vol.24(S1), pp.980.6-980.6
04/2010
DOI: 10.1096/fasebj.24.1_supplement.980.6
Abstract
Transgenic mice expressing a vascular muscle‐specific dominant negative mutant of PPARG (S‐P467L) develop hypertension and aortic dysfunction, supporting a protective role for PPARG in the vasculature. Aortic rings from S‐P467L mice displayed impaired vasodilation to acetylcholine (Ach) and sodium nitroprusside (SNP); and augmented contraction to endothelin‐1 (10nM ET‐1; 0.54±0.04g vs 0.16±0.03g non‐transgenic, NT. P<0.01) that was blocked by pre‐incubation with a Rho‐kinase inhibitor (1μM Y‐27632 + 10nM ET‐1; 0.13±0.02g vs 0.03±0.02g NT). Maximal contraction to PGF2α or KCl was not altered. We tested the role of basal nitric oxide (NO) as an endogenousinhibitor of RhoA/Rho‐kinase signaling. The level of total and p‐Ser1177 eNOS protein did not differ between S‐P467L and NT aorta. NOS inhibition (L‐NAME 100μM) increased contraction of S‐P467L aorta to ET‐1 (1.30±0.06g) to a greater degree than NT (0.50±0.05g, P<0.01). Similar results were observed for PGF2α and KCl. Rho‐kinase‐dependent phosphorylation of MYPT was enhanced in S‐P467L aorta (172±10% of NT, P<0.01). Pre‐incubation with Rho‐kinase inhibitor (1μM Y‐27632) significantly improved relaxation responses to Ach and SNP in S‐P467L aorta, but did not affect NT. We conclude that interference with PPARG in vascular muscle promotes aortic constriction through elevated Rho‐kinase activity, which is inhibited by endogenous NO.
Details
- Title: Subtitle
- Interference with Peroxisome Proliferator Activated Receptor Gamma (PPARG) in smooth muscle causes aortic dysfunction via a Rho‐kinase‐dependent mechanism
- Creators
- Christopher James Pelham - Department of Internal MedicineUniversity of IowaIowa CityIAPimonrat Ketsawatsomkron - Department of Internal MedicineUniversity of IowaIowa CityIASeverine Groh - Department of Internal MedicineUniversity of IowaIowa CityIAWillem J. Lange - University of IowaFrank M. Faraci - University of IowaCurt D. Sigmund - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.24(S1), pp.980.6-980.6
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.24.1_supplement.980.6
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 04/2010
- Academic Unit
- Molecular Physiology and Biophysics; Neuroscience and Pharmacology; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984304731402771
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