Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1.
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.
Wang
Ningning
N
Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA.
Yang
Guangrui
G
Jia
Zhanjun
Z
Zhang
Hui
H
Aoyagi
Toshinori
T
Soodvilai
Sunhapas
S
Symons
J David
JD
Schnermann
Jurgen B
JB
Gonzalez
Frank J
FJ
Litwin
Sheldon E
SE
Yang
Tianxin
T
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D003624:Darkness; D004435:Eating; D006339:Heart Rate; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D000077154:Rosiglitazone; D045162:Thiazolidinediones; C538961:Bmal1 protein, mouse