Rosiglitazone Restores Endothelial Dysfunction in a Rat Model of Metabolic Syndrome Through PPARγ- and PPARδ-Dependent Phosphorylation of Akt and ENOS

Overview

Journal PPAR Res

Publisher Wiley

Date 2011 Dec 23

PMID 22190906

Citations 6

Authors

Zhigang Zhao

Zhidan Luo

Peijian Wang

Jing Sun

Hao Yu

Tingbing Cao

Yinxing Ni

Jing Chen

Zhencheng Yan

Daoyan Liu

Zhiming Zhu

Affiliations

Soon will be listed here.

Abstract

Vascular endothelial dysfunction has been demonstrated in metabolic syndrome (MS). Chronic administration of rosiglitazone ameliorates endothelial dysfunction through PPARγ-mediated metabolic improvements. Recently, studies suggested that single dose of rosiglitazone also has direct vascular effects, but the mechanisms remain uncertain. Here we established a diet-induced rat model of MS. The impaired vasorelaxation in MS rats was improved by incubating arteries with rosiglitazone for one hour. Importantly, this effect was blocked by either inhibition of PPARγ or PPARδ. In cultured endothelial cells, acute treatment with rosiglitazone increased the phosphorylation of Akt and eNOS and the production of NO. These effects were also abolished by inhibition of PPARγ, PPARδ, or PI3K. In conclusion, rosiglitazone improved endothelial function through both PPARγ- and PPARδ-mediated phosphorylation of Akt and eNOS, which might help to reconsider the complex effects and clinical applications of rosiglitazone.

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