Interference with PPARgamma signaling causes cerebral vascular dysfunction, hypertrophy, and remodeling.

ABSTRACT: The transcription factor PPARgamma is expressed in endothelium and vascular muscle where it may exert antiinflammatory and antioxidant effects. We tested the hypothesis that PPARgamma plays a protective role in the vasculature by examining vascular structure and function in heterozygous knockin mice expressing the P465L dominant negative mutation in PPARgamma (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(2alpha), 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

SUBMITTER: Beyer AM 

PROVIDER: S-EPMC2408877 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature