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


METHODS
Primary human aortic endothelial cells (HAECs) were divided into three groups: a normal glucose (NG) group, HG group, and irbesartan (1 microM)-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 alpha-SMA were detected by RT-PCR and Western blot.


RESULTS
The 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 alpha-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).


CONCLUSIONS
These findings suggest a novel mechanism in HG-induced endothelial damage via the mediation of the EndMT by angiotensin II, which was inhibited by Irbesartan.
Tang
Rining
R
Institute of Nephrology, Zhong Da Hospital, Southeast University, Nanjing 210009, China.
Li
Qing
Q
Lv
Linli
L
Dai
Houyong
H
Zheng
Min
M
Ma
Kunling
K
Liu
Bicheng
B
D000199:Actins / Q000235:genetics; D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D001011:Aorta / Q000166:cytology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D000077405:Irbesartan; D008648:Mesoderm / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D000071999:S100 Calcium-Binding Protein A4; D013777:Tetrazoles / Q000494:pharmacology
D000199:Actins; D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D013777:Tetrazoles; D000804:Angiotensin II; C077591:S100A4 protein, human; D005947:Glucose; D000077405:Irbesartan