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

Cardiovasc Res. 2007 Oct 1;76(1):29-40. doi: 10.1016/j.cardiores.2007.05.026. Epub 2007 Jun 6.


Objective: Hydrogen sulfide (H(2)S) 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 (H(2)S donor) concentration-dependently (10-20 micromol/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 micromol/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 micromol kg(-1) day(-1)) significantly promoted neovascularization in vivo in mice.

Conclusion: The present study reports a novel proangiogenic role of H(2)S which is dependent on activation of Akt.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Cell Adhesion / drug effects
  • Cell Migration Assays
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chromones / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Female
  • Humans
  • Hydrogen Sulfide / pharmacology*
  • Inhibitor of Apoptosis Proteins
  • Integrin alpha2 / analysis
  • Integrin alpha2 / metabolism
  • Integrin beta1 / analysis
  • Integrin beta1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / analysis
  • Microtubule-Associated Proteins / metabolism
  • Morpholines / pharmacology
  • Neovascularization, Physiologic / drug effects*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Repressor Proteins
  • Staining and Labeling
  • Stimulation, Chemical
  • Survivin
  • Tissue Culture Techniques
  • Wortmannin
  • Wound Healing / drug effects


  • Androstadienes
  • Birc5 protein, mouse
  • Chromones
  • Inhibitor of Apoptosis Proteins
  • Integrin alpha2
  • Integrin beta1
  • Microtubule-Associated Proteins
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Repressor Proteins
  • Survivin
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt
  • Wortmannin
  • Hydrogen Sulfide