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2015 ; 8
(3
): 2505-14
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Local renin-angiotensin system regulates hypoxia-induced vascular endothelial
growth factor synthesis in mesenchymal stem cells
#MMPMID26045756
Fan Y
; Wang L
; Liu C
; Zhu H
; Zhou L
; Wang Y
; Wu X
; Li Q
Int J Clin Exp Pathol
2015[]; 8
(3
): 2505-14
PMID26045756
show ga
The use of mesenchymal stem cell (MSC) transplantation for ischemic heart disease
has been reported for several years. The main mechanisms responsible for the
efficacy of this technique include the differentiation of MSCs into
cardiomyocytes and endothelial cells, as well as paracrine effects. However, the
differentiation rates of MSCs are very low, and the differentiated cells are not
mature. In addition, MSCs undergo massive cell death within a few days after
transplantation to the ischemic myocardium. Paracrine effects may thus play a
major role in MSCs transplantation. Angiotensin II (Ang II) is known to be
produced locally in the ischemic myocardium, but the effects of hypoxia on the
local renin-angiotensin system (RAS) in MSCs, and the role of the RAS in
hypoxia-induced vascular endothelial growth factor (VEGF) secretion remain
unknown. In this study, we demonstrated that hypoxia stimulated the local RAS in
MSCs, while pretreatment with the Ang II type 1 (AT1) receptor antagonist
losartan reduced hypoxia-induced hypoxia-inducible factor 1? (HIF-1?) and VEGF
production. The ERK1/2 inhibitor U0126 and the Akt inhibitor LY294002 also
inhibited hypoxia-induced HIF-1? and VEGF production. Overall, these results
indicate that the local RAS in MSCs regulates hypoxia-induced VEGF production
through ERK1/2, Akt and HIF-1? pathways via the AT1 receptor.