@article{d5b7b1bfef58427a891cd0b15fb788b1,
title = "Interference with PPARγ Function in Smooth Muscle Causes Vascular Dysfunction and Hypertension",
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.",
keywords = "HUMDISEASE, SIGNALING",
author = "Halabi, {Carmen M.} and Beyer, {Andreas M.} and {de Lange}, {Willem J.} and Keen, {Henry L.} and Baumbach, {Gary L.} and Faraci, {Frank M.} and Sigmund, {Curt D.}",
note = "Funding Information: This work was supported by grants from the NIH (HL48058, HL61446, and HL55006 to C.D.S.; HL38901, HL62984, and NS24621 to F.M.F.; and T32 GM008629 to C.M.H. as part of the Genetics Training Program) and the American Heart Association (0415460Z to A.M.B.). S-PPARγ mice were generated and maintained at the University of Iowa Transgenic Animal Facility, supported by the Carver College of Medicine. We would like to thank K. Rahmouni, M.J. Ryan, and J. Grobe for advice; C. Allamargot at the University of Iowa Central Microscopy Research Facility for performing in situ hybridization; R. Bianco for initial construct generation; D. Davis for mouse surgery; R. Weiss (funded by NIH grant RR017369) for performing echocardiography; and G. Owens for the gift of the smooth muscle myosin heavy chain promoter. We gratefully acknowledge the generous research support of the Roy J. Carver Trust. ",
year = "2008",
month = mar,
day = "5",
doi = "10.1016/j.cmet.2007.12.008",
language = "English",
volume = "7",
pages = "215--226",
journal = "Cell metabolism",
issn = "1550-4131",
number = "3",
}