The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation

  • Cai W
  • Wang M
  • Moore P
 et al. 
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Objective: Hydrogen sulfide (H2S) has been reported to be a gasotransmitter which regulates cardiovascular homeostasis. The present study aims to examine the hypothesis that hydrogen sulfide is able to promote angiogenesis. Methods: Angiogenesis was assessed using in vitro parameters (i.e. endothelial cell proliferation, adhesion, transwell migration assay, scratched wound healing and formation of tube-like structure) and in vivo by assessing neovascularization in mice. Phosphorylation of Akt was measured using Western blot analysis. Results: Exogenously administered NaHS (H2S donor) concentration-dependently (10-20 μmol/l) increased cell growth, migration, scratched wound healing and tube-like structure formation in cultured endothelial cells. These effects of NaHS on endothelial wound healing and tube-like structure formation were prevented by either the phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002 (5 μmol/l) or transfection of a dominant-negative mutant of Akt. NaHS increased Akt phosphorylation and this effect was also blocked by either LY 294002 or wortmannin (25 nmol/l). NaHS did not significantly alter the levels of vascular endothelial growth factor, mRNA expression of fibroblast growth factor and angiopoietin-1, or nitric oxide metabolites. NaHS treatment (10 and 50 μmol kg- 1day- 1) significantly promoted neovascularization in vivo in mice. Conclusion: The present study reports a novel proangiogenic role of H2S which is dependent on activation of Akt. © 2007 European Society of Cardiology.

Author-supplied keywords

  • Angiogenesis
  • Endothelial cells
  • Migration

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  • Jenn-Kun KuoJenn-Kun Kuo

  • Wen Jie Cai

  • Ming Jie Wang

  • Philip Keith Moore

  • Hui Ming Jin

  • Tai Yao

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