Copyright © 2007, European Society of Cardiology
The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation
aDepartment of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China
bCardiovascular Biology Research Group, Department of Pharmacology, National University of Singapore, Singapore
*Corresponding author. Department of Physiology and Pathophysiology Fudan University Shanghai Medical College 138 Yi Xue Yuan Road Shanghai, 200032, China. Tel.: +86 21 5423 7098; fax: +86 21 5423 7098. yczhu{at}shmu.edu.cn
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–1 day–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.
KEYWORDS Angiogenesis; Endothelial cells; Migration
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