Vascular endothelial growth factor promotes cardiac stem cell migration via the PI3K/Akt pathway.

Abstract:

:VEGF is a major inducer of angiogenesis. However, the homing role of VEGF for cardiac stem cells (CSCs) is unclear. In in vitro experiments, CSCs were isolated from the rat hearts, and a cellular migration assay was performed using a 24-well transwell system. VEGF induced CSC migration in a concentration-dependent manner, and SU5416 blocked this. Western blot analysis showed that the phosphorylated Akt was markedly increased in the VEGF-treated CSCs and that inhibition of pAkt activity significantly attenuated the VEGF-induced the migration of CSCs. In in vivo experiments, rat heart myocardial infarction (MI) was induced by left coronary artery ligation. One week after MI, the adenoviral vector expressing hVEGF165 and LacZ genes were injected separately into the infarcted myocardium at four sites before endomyocardial transplantation of 2x10(5) PKH26 labeled CSCs (50 muL) at atrioventricular groove. One week after CSC transplantation, RT-PCR, immunohistochemical staining, Western blot, and ELISA analysis were performed to detect the hVEGF mRNA and protein. The expression of hVEGF mRNA and protein was significantly increased in the infarcted and hVEGF165 transfected rat hearts, accompanied by an enhanced PI3K/Ak activity, a greater accumulation of CSCs in the infarcted region, and an improvement in cardiac function. The CSC accumulation was inhibited by either the VEGF receptor blocker SU5416 or the PI3K/Ak inhibitor wortmannin. VEGF signaling may mediate the migration of CSCs via activation of PI3K/Akt.

journal_name

Exp Cell Res

authors

Tang J,Wang J,Kong X,Yang J,Guo L,Zheng F,Zhang L,Huang Y,Wan Y

doi

10.1016/j.yexcr.2009.09.026

subject

Has Abstract

pub_date

2009-12-10 00:00:00

pages

3521-31

issue

20

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(09)00416-9

journal_volume

315

pub_type

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