Published in
Cell Press, Cell Metabolism, 6(8), p. 482-491, 2008
DOI: 10.1016/j.cmet.2008.10.009
Links
Tools
Vascular PPARγ Controls Circadian Variation in Blood Pressure and Heart Rate through Bmal1
,
Zhanjun Jia,
Hui Zhang,
Toshinori Aoyagi,
Sunhapas Soodvilai,
J. David Symons,
J. David Symons,
Jurgen B. Schnermann,
Frank J. Gonzalez,
Sheldon E. Litwin,
Others,
Tianxin Yang
Full text: Download
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.