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A protective role of ciglitazone in ox-LDL-induced rat microvascular endothelial cells via modulating PPAR gamma-dependent AMPK/eNOS pathway 期刊论文

编号：

4beec697-646e-4fe5-b3cf-c4e2bc40dd68
作者：

Xu, Lei^[1,2];Wang, Shijun^[1,2];Li, Bingyu^[1];Sun, Aijun(孙爱军)^[1,2]Zou, Yunzeng(邹云增)^[1,2]Ge, Junbo(葛均波)*^[1,2]
语种：

English
期刊：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE ISSN：1582-4934 2015 年 19 卷 1 期 (92 - 102) ; JAN
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关键词：

AMPK eNOS PPAR endothelial cells LOX-1 angiogenesis
摘要：

Thiazolidinediones, the antidiabetic agents such as ciglitazone, has been proved to be effective in limiting atherosclerotic events. However, the underlying mechanism remains elucidative. Ox-LDL receptor-1 (LOX-1) plays a central role in ox-LDL-mediated atherosclerosis via endothelial nitric oxide synthase (eNOS) uncoupling and nitric oxide reduction. Therefore, we tested the hypothesis that ciglitazone, the PPAR agonist, protected endothelial cells against ox-LDL through regulating eNOS activity and LOX-1 signalling. In the present study, rat microvascular endothelial cells (RMVECs) were stimulated by ox-LDL. The impact of ciglitazone on cell apoptosis and angiogenesis, eNOS expression and phosphorylation, nitric oxide synthesis and related AMPK, Akt and VEGF signalling pathway were observed. Our data showed that both eNOS and Akt phosphorylation, VEGF expression and nitric oxide production were significantly decreased, RMVECs ageing and apoptosis increased after ox-LDL induction for 24hrs, all of which were effectively reversed by ciglitazone pre-treatment. Meanwhile, phosphorylation of AMP-activated protein kinase (AMPK) was suppressed by ox-LDL, which was also prevented by ciglitazone. Of interest, AMPK inhibition abolished ciglitazone-mediated eNOS function, nitric oxide synthesis and angiogenesis, and increased RMVECs ageing and apoptosis. Further experiments showed that inhibition of PPAR significantly suppressed AMPK phosphorylation, eNOS expression and nitric oxide production. Ciglitazone-mediated angiogenesis and reduced cell ageing and apoptosis were reversed. Furthermore, LOX-1 protein expression in RMVECs was suppressed by ciglitazone, but re-enhanced by blocking PPAR or AMPK. Ox-LDL-induced suppression of eNOS and nitric oxide synthesis were largely prevented by silencing LOX-1. Collectively, these data demonstrate that ciglitazone-mediated PPAR activation suppresses LOX-1 and moderates AMPK/eNOS pathway, which contributes to endothelial cell survival and function preservation.
推荐引用方式
GB/T 7714：

Xu Lei,Wang Shijun,Li Bingyu, et al. A protective role of ciglitazone in ox-LDL-induced rat microvascular endothelial cells via modulating PPAR gamma-dependent AMPK/eNOS pathway [J].JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2015,19(1):92-102.
APA：

Xu Lei,Wang Shijun,Li Bingyu,Sun Aijun,&Ge Junbo.(2015).A protective role of ciglitazone in ox-LDL-induced rat microvascular endothelial cells via modulating PPAR gamma-dependent AMPK/eNOS pathway .JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,19(1):92-102.
MLA：

Xu Lei, et al. "A protective role of ciglitazone in ox-LDL-induced rat microvascular endothelial cells via modulating PPAR gamma-dependent AMPK/eNOS pathway" .JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 19,1(2015):92-102.

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