Vascular PPARγ Controls Circadian Variation in Blood Pressure and Heart Rate through Bmal1

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Abstract

Thiazolidinediones (TZDs) are PPARγ activators that exhibit vasculoprotective properties. To determine the vascular function of PPARγ, 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. PPARγ 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 PPARγ target gene. These studies have uncovered a role for vascular PPARγ as a peripheral factor participating in regulation of cardiovascular rhythms. © 2008 Elsevier Inc. All rights reserved.

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Wang, N., Yang, G., Jia, Z., Zhang, H., Aoyagi, T., Soodvilai, S., … Yang, T. (2008). Vascular PPARγ Controls Circadian Variation in Blood Pressure and Heart Rate through Bmal1. Cell Metabolism, 8(6), 482–491. https://doi.org/10.1016/j.cmet.2008.10.009

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