期刊
CELL METABOLISM
卷 7, 期 3, 页码 215-226出版社
CELL PRESS
DOI: 10.1016/j.cmet.2007.12.008
关键词
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资金
- NCRR NIH HHS [K26 RR017369, RR017369] Funding Source: Medline
- NHLBI NIH HHS [R01 HL076421, P01 HL062984-06A10005, HL38901, R01 HL048058, R01 HL076421-02, R01 HL076421-03, R01 HL076421-04, R37 HL048058, P01 HL062984-070005, R01 HL038901, P01 HL062984, R01 HL061446, R01 HL076421-01, HL55006, HL61446, HL62984, P50 HL055006, HL48058] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008629, T32 GM007337, T32GM008629] Funding Source: Medline
- NINDS NIH HHS [NS24621, P01 NS024621-160017, P01 NS024621-119004, P01 NS024621-139004, P01 NS024621-159004, P01 NS024621-169004, P01 NS024621-129004, P01 NS024621, P01 NS024621-149004] Funding Source: Medline
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated transcription factor that plays a critical role in metabolism. Thiazolidinediones, high-affinity PPAR gamma ligands used clinically to treat type II diabetes, have been reported to lower blood pressure and provide other cardiovascular benefits. Some mutations in PPAR gamma (PPARG) cause type II diabetes and severe hypertension. Here we tested the hypothesis that PPAR gamma in vascular muscle plays a role in the regulation of vascular tone and blood pressure. Transgenic mice expressing dominant-negative mutations in PPAR gamma 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 PPAR gamma 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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