title: Akt-centered amplification loop plays a critical role in vascular endothelial growth factor/stromal cell-derived factor 1-α cross-talk and cardioprotection.
abstract: 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Guo
authors.forename: Dian-Xin
authors.initials: DX
authors.lastname: Zhang
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Li
authors.forename: Zhi-Jing
authors.initials: ZJ
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Hai-Chang
authors.initials: HC
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006861:Hydrogen Peroxide / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; D042461:Vascular Endothelial Growth Factor A; D006861:Hydrogen Peroxide