title: Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1.
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.
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Ningning
authors.initials: N
authors.lastname: Wang
authors.forename: Guangrui
authors.initials: G
authors.lastname: Yang
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Toshinori
authors.initials: T
authors.lastname: Aoyagi
authors.forename: Sunhapas
authors.initials: S
authors.lastname: Soodvilai
authors.forename: J David
authors.initials: JD
authors.lastname: Symons
authors.forename: Jurgen B
authors.initials: JB
authors.lastname: Schnermann
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Sheldon E
authors.initials: SE
authors.lastname: Litwin
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: 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
chemical_list: 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