Akt-centered amplification loop plays a critical role in vascular endothelial growth factor/stromal cell-derived factor 1-αcross-talk and cardioprotection  

作　　者：GUO Wen-yi ZHANG Dian-xin LI Wei-jie ZHAO Zhi-jing LIU Bing WANG Hai-chang LI Fei 

机构地区：[1]Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi＇an, Shaanxi 710032, China

出　　处：《Chinese Medical Journal》2011年第22期3800-3805,共6页中华医学杂志（英文版）

基　　金：This study was supported by a grant from the National Natural Science Foundation of China （No. 30600580）.

摘　　要：Background Vascular endothelial growth factor （VEGF） is one of major mediators of angiogenesis and survival factor in some tissue, however, its direct effects on cardiomyocytes remain poorly understood. Methods Rat neonatal ventricular myocytes were cultured in vitro. Akt phosphorylation was measured by Western blotting; the expression of stromal cell-derived factor α（SDF-1α）/CXCR4 axis was evaluated by real-time PCR and Western blotting. LY294002 and AMD3100 were used to interfere with the signaling of VEGF and SDF-1α/CXCR4 axis. Cardiac myocytes viability and injury were evaluated by trypan blue staining and lactate dehydrogenase （LDH） release. Results Treatment of neonatal rat ventricular myocytes with VEGF induced phosphorylation of Akt in a dose and FIk-1 dependent manner. VEGF attenuated H202 induced cardiac myocyte death. The phosphoinositol-3-kinase （PI3K） inhibitor, LY294002 and FIk-1 antibody abolished the beneficial effects of VEGF on H202 induced cell death. In the mean time SDF-1α-CXCR4 axis was up-regulated by VEGF through PI3K-Akt signaling and contributed to the protective effects of VEGF on H202 induced cell death. Interestingly, SDF-1α also promoted production of VEGF in cultured cardiac myocytes and LY294002 reversed the up-reguLation of VEGF induced by SDF-1α. Conclusion VEGF has direct protective effects on cardiomyocytes; a crosstalk between VEGF and SDF-1α through PI3K-Akt serves a survival role in cardiomvocvtes in vitro.Background Vascular endothelial growth factor （VEGF） is one of major mediators of angiogenesis and survival factor in some tissue, however, its direct effects on cardiomyocytes remain poorly understood. Methods Rat neonatal ventricular myocytes were cultured in vitro. Akt phosphorylation was measured by Western blotting; the expression of stromal cell-derived factor α（SDF-1α）/CXCR4 axis was evaluated by real-time PCR and Western blotting. LY294002 and AMD3100 were used to interfere with the signaling of VEGF and SDF-1α/CXCR4 axis. Cardiac myocytes viability and injury were evaluated by trypan blue staining and lactate dehydrogenase （LDH） release. Results Treatment of neonatal rat ventricular myocytes with VEGF induced phosphorylation of Akt in a dose and FIk-1 dependent manner. VEGF attenuated H202 induced cardiac myocyte death. The phosphoinositol-3-kinase （PI3K） inhibitor, LY294002 and FIk-1 antibody abolished the beneficial effects of VEGF on H202 induced cell death. In the mean time SDF-1α-CXCR4 axis was up-regulated by VEGF through PI3K-Akt signaling and contributed to the protective effects of VEGF on H202 induced cell death. Interestingly, SDF-1α also promoted production of VEGF in cultured cardiac myocytes and LY294002 reversed the up-reguLation of VEGF induced by SDF-1α. Conclusion VEGF has direct protective effects on cardiomyocytes; a crosstalk between VEGF and SDF-1α through PI3K-Akt serves a survival role in cardiomvocvtes in vitro.

关 键 词：vascular endothelial growth factor cardiomyocyte  stromal cell-derived factor a survival PI3K-Akt 

分 类 号：Q78[生物学—分子生物学] Q987