Epigallocatechin gallate inhibits angiotensin II- induced endothelial barrier dysfunction via inhibition of the p38 MAPK/HSP27 pathway  

作　　者：Dan YANG Jing LIU Cui TIAN Yong ZENG Yue-hong ZHENG Quan FANG Hui-hua LI 

机构地区：[1]Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 [2]Department of Cardiology Peking Union Medical Hospital, Beijing 100730, China [3]Department of Vascular Surgery, Peking Union Medical Hospital, Beijing 100730, China

出　　处：《Acta Pharmacologica Sinica》2010年第10期1401-1406,共6页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by grants from the National Natural Science Foundation of China （HL, 2006CB910306） and the 111 project （HL, B08007）.

摘　　要：Aim： To investigate the effect of epigallocatechin gallate （EGCG） on angiotensin II （Ang li）-induced stress fiber formation and hyperper- meability in endothelial cells. Methods： Human umbilical vein endothelial cells （HUVECs） were treated with Ang II in the absence or presence of EGCG or mitogenactivated protein kinases （MAPKs） inhibitors. The resulting stress fibers were stained with rhodamine-phalloidin and examined using confocal microscopy. The permeability of the endothelium was tested with fluorescein-isothiocyanate labeled bovine serum albumin （FITC-BSA）, and the phosphorylation levels of several proteins were determined using Western blot analysis. Results： Ang II （1-100 nmol/L） treatment markedly provoked stress fiber formation and hyperpermeability in HUVECs in a time- and dose-dependent manner. These effects were abolished by pretreatment with the p38 MAPK inhibitor SB203580 10 pmol/L, indicating that the Ang II-induced endothelial barrier dysfunction was via activation of the p38 MAPK/HSP27 pathway. Furthermore, treatment with EGCG （5-25） pmol/L inhibited Ang II-induced activation of the p38 MAPK/HSP27 pathway, thereby reducing endothelial stress fiber formation and hyperpermeability. Conclusion： Our data demonstrate that EGCG inhibits Ang II-induced endothelial stress fiber formation and hyperpermeability via inactivation of p38 MAPK/HSP27 pathway, and suggest that EGCG may protect against endothelial barrier dysfunction and injury.Aim： To investigate the effect of epigallocatechin gallate （EGCG） on angiotensin II （Ang li）-induced stress fiber formation and hyperper- meability in endothelial cells. Methods： Human umbilical vein endothelial cells （HUVECs） were treated with Ang II in the absence or presence of EGCG or mitogenactivated protein kinases （MAPKs） inhibitors. The resulting stress fibers were stained with rhodamine-phalloidin and examined using confocal microscopy. The permeability of the endothelium was tested with fluorescein-isothiocyanate labeled bovine serum albumin （FITC-BSA）, and the phosphorylation levels of several proteins were determined using Western blot analysis. Results： Ang II （1-100 nmol/L） treatment markedly provoked stress fiber formation and hyperpermeability in HUVECs in a time- and dose-dependent manner. These effects were abolished by pretreatment with the p38 MAPK inhibitor SB203580 10 pmol/L, indicating that the Ang II-induced endothelial barrier dysfunction was via activation of the p38 MAPK/HSP27 pathway. Furthermore, treatment with EGCG （5-25） pmol/L inhibited Ang II-induced activation of the p38 MAPK/HSP27 pathway, thereby reducing endothelial stress fiber formation and hyperpermeability. Conclusion： Our data demonstrate that EGCG inhibits Ang II-induced endothelial stress fiber formation and hyperpermeability via inactivation of p38 MAPK/HSP27 pathway, and suggest that EGCG may protect against endothelial barrier dysfunction and injury.

关 键 词：angiotensin II epigallocatechin gallate endothelial barrier function mitogen-activated protein kinases heat-shock protein 27 

分 类 号：Q463[生物学—生理学] Q25