title: Rosiglitazone Restores Endothelial Dysfunction in a Rat Model of Metabolic Syndrome through PPARγ- and PPARδ-Dependent Phosphorylation of Akt and eNOS.
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.
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Luo
authors.forename: Peijian
authors.initials: P
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Tingbing
authors.initials: T
authors.lastname: Cao
authors.forename: Yinxing
authors.initials: Y
authors.lastname: Ni
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Zhencheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu