Hydrogen sulfide is an endogenous stimulator of angiogenesis

Andreas Papapetropoulos, Anastasia Pyriochou, Zaid Altaany, Guangdong Yang, Antonia Marazioti, Zongmin Zhou, Mark G. Jeschke, Ludwik K. Branski, David N. Herndon, Rui Wang, Csaba Szabó

Research output: Contribution to journalArticlepeer-review

732 Scopus citations


The goal of the current study was to investigate the role of exogenous and endogenous hydrogen sulfide (H2S) on neovascularization and wound healing in vitro and in vivo. Incubation of endothelial cells (ECs) with H 2S enhanced their angiogenic potential, evidenced by accelerated cell growth, migration, and capillary morphogenesis on Matrigel. Treatment of chicken chorioallantoic membranes (CAMS) with H2S increased vascular length. Exposure of ECs to H2S resulted in increased phosphorylation of Akt, ERK, and p38. The KATP channel blocker glibenclamide or the p38 inhibitor SB203580 abolished H2S-induced EC motility. Since glibenclamide inhibited H2S-triggered p38 phosphorylation, we propose that KATP channels lay upstream of p38 in this process. When CAMs were treated with H2S biosynthesis inhibitors dl-propylargylglycine or beta-cyano-L-alanine, a reduction in vessel length and branching was observed, indicating that H2S serves as an endogenous stimulator of the angiogenic response. Stimulation of ECs with vascular endothelial growth factor (VEGF) increased H2S release, while pharmacological inhibition of H2S production or KATP channels or silencing of cystathionine gamma-lyase (CSE) attenuated VEGF signaling and migration of ECs. These results implicate endothelial H2S synthesis in the pro-angiogenic action of VEGF. Aortic rings isolated from CSE knockout mice exhibited markedly reduced microvessel formation in response to VEGF when compared to wild-type littermates. Finally, in vivo, topical administration of H2S enhanced wound healing in a rat model, while wound healing was delayed in CSE-/- mice. We conclude that endogenous and exogenous H2S stimulates EC-related angiogenic properties through a K ATP channel/MAPK pathway.

Original languageEnglish (US)
Pages (from-to)21972-21977
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number51
StatePublished - Dec 22 2009


  • Blood vessels
  • Endothelial cell
  • MAP kinases

ASJC Scopus subject areas

  • General


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