Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1.

Wang, Ningning; Yang, Guangrui; Jia, Zhanjun; Zhang, Hui; Aoyagi, Toshinori; Soodvilai, Sunhapas; Symons, J David; Schnermann, Jurgen B et al. · Cell Metab · 2008

basic_science · Level V

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Abstract

Thiazolidinediones (TZDs) are PPARgamma activators that exhibit vasculoprotective properties. To determine the vascular function of PPARgamma, we analyzed Tie2Cre/flox and SM22Cre/flox mice. Unexpectedly, both knockout strains exhibited a significant reduction of circadian variations in blood pressure and heart rate in parallel with diminished variations in urinary norepinephrine/epinephrine excretion and impaired rhythmicity of the canonical clock genes, including Bmal1. PPARgamma expression in the aorta exhibited a robust rhythmicity with a more than 20-fold change during the light/dark cycle. Rosiglitazone treatment induced aortic expression of Bmal1 mRNA, and ChIP and promoter assays revealed that Bmal1 is a direct PPARgamma target gene. These studies have uncovered a role for vascular PPARgamma as a peripheral factor participating in regulation of cardiovascular rhythms.

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