Angiotensin II mediates the high-glucose-induced endothelial-to-mesenchymal transition in human aortic endothelial cells

Cardiovascular Diabetology

Original Investigation

Qing Li¹  Bicheng Liu¹  Rining Tang¹  Houyong Dai¹  Kunling Ma¹  Min Zheng¹  Linli Lv¹ 

[1] Institute of Nephrology, Zhong Da Hospital, Southeast University, 210009, Nanjing, China;

关键词: High Glucose;    Irbesartan;    Cardiac Fibrosis;    Renal Fibrose;    Human Aortic Endothelial Cell;   

DOI  :  10.1186/1475-2840-9-31

 received in 2010-06-17, accepted in 2010-07-27,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSubstantial evidence suggests that high glucose (HG) causes endothelial cell damage; however, the potential mechanism therein has yet to be clarified. The aim of this study was to investigate the influence of HG on the endothelial-to-mesenchymal transition (EndMT) and its relevance to the activation of the renin-angiotensin system.MethodsPrimary human aortic endothelial cells (HAECs) were divided into three groups: a normal glucose (NG) group, HG group, and irbesartan (1 μM)-treated (HG+irbesartan) group. The concentration of angiotensin II in the supernatant was detected by radioimmunoassay. Pathological changes were investigated using fluorescence microscopy and electron microscopy. Immunofluorescence staining was performed to detect the co-expression of CD31 and fibroblast markers, such as fibroblast-specific protein 1 (FSP1). The expressions of FSP1 and α-SMA were detected by RT-PCR and Western blot.ResultsThe treatment of HAECs in the HG group resulted in significant increases in the expressions of FSP1 and angiotensin II in dose-and time-dependent manners. The incubation of HAECs exposure to HG resulted in a fibroblast-like phenotype, wherein increased microfilamentation and a roughened endoplasmic reticulum structure were observed in the cytoplasm. The expressions of FSP1 and α-SMA were significantly increased in the HG group, and these changes were inhibited by irbesartan treatment (P < 0.05). Double staining of the HAECs indicated a co-localization of CD31 and FSP1 and that some cells acquired spindle-shaped morphologies and a loss of CD31 staining; however, treatment with irbesartan attenuated the expression of EndMT (P < 0.05).ConclusionsThese findings suggest a novel mechanism in HG-induced endothelial damage via the mediation of the EndMT by angiotensin II, which was inhibited by Irbesartan.

【 授权许可】

Unknown   
© Tang et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.