The Role of RhoA in Neovascular-Related Functions of Endothelial Progenitor Cells Induced by AngiotensinⅡ.
BACKGROUND/AIMS
Interference with endothelial progenitor cell (EPC) neovascularization is a novel therapeutic target for neovascular-related diseases. Angiotensin Ⅱ (Ang Ⅱ) was found to enhance new vessel formation and aggravated neovascular-related diseases. In this study, we investigated the effects of Ang Ⅱ on EPC neovascular-related functions and explored the underlying mechanisms.


METHODS
EPCs were cultured from bone marrow derived mononuclear cells. The effects of Ang Ⅱ on EPC proliferation, adhesion, migration, and in vitro tube formation were investigated using the MTT assay, adhesion assay, transwell chamber assay, and in vitro tube formation assay respectively. The underlying mechanisms were explored using Western blotting assay.


RESULTS
EPC adhesion, migration and in vitro tube formation were promoted by Ang Ⅱ, and the effects were reversed by RhoA/Rho-associated kinases (ROCK) signaling pathway inhibitors including C3 exoenzyme, GGTI-286 and Y-27632. The active form of RhoA was up-regulated by Ang Ⅱ and this effect was abolished by C3 exoenzyme. Moreover, RhoA silencing resulted in a notable inhibition of EPC adhesion, migration and in vitro tube formation, suggesting that RhoA activation played a pivotal role in Ang Ⅱ angiogenic effect. The results also demonstrated that phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun-NH2 kinase was elevated by Ang Ⅱ and attenuated by C3 exoenzyme, GGTI-286 and Y-27632. The enhancing effects of Ang Ⅱ on EPC adhesion, migration and in vitro vasculogenesis were reversed by p38 inhibitor SB202190 and JNK inhibitor SP600125.


CONCLUSION
Ang Ⅱ may enhance EPC neovascular-related functions through activating RhoA/ ROCK and MAPK signaling pathway.
['Yang|Jin-Xiu|JX|', 'Pan|Yan-Yun|YY|', 'Chen|Bin|B|', 'Qiu|Yuan-Gang|YG|', 'Mao|Wei|W|', 'Hu|Shen-Jiang|SJ|']
D000804:Angiotensin II D000818:Animals D002448:Cell Adhesion D002465:Cell Movement D066026:Endothelial Progenitor Cells D020935:MAP Kinase Signaling System D008297:Male D009389:Neovascularization, Pathologic D051381:Rats D017207:Rats, Sprague-Dawley D020741:rho GTP-Binding Proteins
Neovascular-related functions Endothelial progenitor cell Signaling pathway RhoA/ROCK