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

被引：208

作者：

Wang, Ningning ^{[1
,2
]}

Yang, Guangrui ^{[1
,2
]}

Jia, Zhanjun ^{[1
,2
]}

Zhang, Hui ^{[1
,2
]}

Aoyagi, Toshinori ^{[1
,2
]}

Soodvilai, Sunhapas ^{[1
,2
]}

Symons, J. David ^{[3
,4
]}

Schnermann, Jurgen B. ^{[5
]}

Gonzalez, Frank J. ^{[6
,7
]}

Litwin, Sheldon E. ^{[1
,2
]}

Yang, Tianxin ^{[1
,2
]}

机构：

[1] Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA

[2] Salt Lake Vet Affairs Med Ctr, Salt Lake City, UT 84132 USA

[3] Univ Utah, Coll Hlth, Salt Lake City, UT 84132 USA

[4] Univ Utah, Div Endocrinol Diabet & Metab, Salt Lake City, UT 84132 USA

[5] NIDDKD, Bethesda, MD 20892 USA

[6] NCI, Bethesda, MD 20892 USA

[7] NIH, Bethesda, MD 20892 USA

来源：

CELL METABOLISM | 2008年 / 8卷 / 06期

关键词：

D O I：

10.1016/j.cmet.2008.10.009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：482 / 491

页数：10

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