Journal
CELL METABOLISM
Volume 8, Issue 6, Pages 482-491Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2008.10.009
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Funding
- Department of Veterans Affairs
- National Institute of Health [RO-1 HL079453]
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Thiazolidinediones (TZDs) are PPAR gamma activators that exhibit vasculoprotective properties. To determine the vascular function of PPAR gamma, we analyzed Tie2-Cre/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. PPAR gamma 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 PPAR gamma target gene. These studies have uncovered a role for vascular PPAR gamma as a peripheral factor participating in regulation of cardiovascular rhythms.
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