Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1

Ningning Wang; Guangrui Yang; Zhanjun Jia; Hui Zhang; Toshinori Aoyagi; Sunhapas Soodvilai; J David Symons; Jurgen B Schnermann; Frank J Gonzalez; Sheldon E Litwin; Tianxin Yang

doi:10.1016/j.cmet.2008.10.009

Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1

Cell Metab. 2008 Dec;8(6):482-91. doi: 10.1016/j.cmet.2008.10.009.

Authors

Ningning Wang¹, Guangrui Yang, Zhanjun Jia, Hui Zhang, Toshinori Aoyagi, Sunhapas Soodvilai, J David Symons, Jurgen B Schnermann, Frank J Gonzalez, Sheldon E Litwin, Tianxin Yang

Affiliation

¹ Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

ARNTL Transcription Factors
Animals
Basic Helix-Loop-Helix Transcription Factors / biosynthesis
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Biological Clocks / drug effects
Biological Clocks / physiology
Blood Pressure*
Cells, Cultured
Circadian Rhythm / genetics
Circadian Rhythm / physiology*
Darkness
Eating
Heart Rate*
Hypoglycemic Agents / administration & dosage
Hypoglycemic Agents / pharmacology
Mice
Mice, Knockout
Mutation
PPAR gamma / biosynthesis
PPAR gamma / genetics
PPAR gamma / metabolism*
Promoter Regions, Genetic
RNA, Messenger / analysis
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Rosiglitazone
Thiazolidinediones / administration & dosage
Thiazolidinediones / pharmacology

Substances

ARNTL Transcription Factors
Bmal1 protein, mouse
Basic Helix-Loop-Helix Transcription Factors
Hypoglycemic Agents
PPAR gamma
RNA, Messenger
Thiazolidinediones
Rosiglitazone

Abstract

Publication types

MeSH terms

Substances

Grants and funding