Akt-centered amplification loop plays a critical role in vascular endothelial growth factor/stromal cell-derived factor 1-α cross-talk and cardioprotection / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 3800-3805, 2011.
Artigo
em Inglês
| WPRIM
| ID: wpr-273972
ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>Treatment of neonatal rat ventricular myocytes with VEGF induced phosphorylation of Akt in a dose and Flk-1 dependent manner. VEGF attenuated H2O2 induced cardiac myocyte death. The phosphoinositol-3-kinase (PI3K) inhibitor, LY294002 and Flk-1 antibody abolished the beneficial effects of VEGF on H2O2 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 H2O2 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.</p><p><b>CONCLUSION</b>VEGF has direct protective effects on cardiomyocytes; a crosstalk between VEGF and SDF-1α through PI3K-Akt serves a survival role in cardiomyocytes in vitro.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Fosforilação
/
Ensaio de Imunoadsorção Enzimática
/
Sobrevivência Celular
/
Células Cultivadas
/
Western Blotting
/
Morte Celular
/
Biologia Celular
/
Miócitos Cardíacos
/
Fator A de Crescimento do Endotélio Vascular
Limite:
Animais
Idioma:
Inglês
Revista:
Chinese Medical Journal
Ano de publicação:
2011
Tipo de documento:
Artigo
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