Hydrogen sulphide and angiogenesis: Mechanisms and applications

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131 Scopus citations

Abstract

In vascular tissues, hydrogen sulphide (H 2S) is mainly produced from L-cysteine by the cystathionine gamma-lyase (CSE) enzyme. Recent studies show that administration of H 2S to endothelial cells in culture stimulates cell proliferation, migration and tube formation. In addition, administration of H 2S to chicken chorioallantoic membranes stimulates blood vessel growth and branching. Furthermore, in vivo administration of H 2S to mice stimulates angiogenesis, as demonstrated in the Matrigel plug assay. Pathways involved in the angiogenic response of H 2S include the PI-3K/Akt pathway, the mitogen activated protein kinase pathway, as well as ATP-sensitive potassium channels. Indirect evidence also suggests that the recently demonstrated role of H 2S as an inhibitor of phosphodiesterases may play an additional role in its pro-angiogenic effect. The endogenous role of H 2S in the angiogenic response has been demonstrated in the chicken chorioallantoic membranes, in endothelial cells in vitro and ex vivo. Importantly, the pro-angiogenic effect of vascular endothelial growth factor (but not of fibroblast growth factor) involves the endogenous production of H 2S. The pro-angiogenic effects of H 2S are also apparent in vivo: in a model of hindlimb ischaemia-induced angiogenesis, H 2S induces a marked pro-angiogenic response; similarly, in a model of coronary ischaemia, H 2S exerts angiogenic effects. Angiogenesis is crucial in the early stage of wound healing. Accordingly, topical administration of H 2S promotes wound healing, whereas genetic ablation of CSE attenuates it. Pharmacological modulation of H 2S-mediated angiogenic pathways may open the door for novel therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)853-865
Number of pages13
JournalBritish Journal of Pharmacology
Volume164
Issue number3
DOIs
StatePublished - Oct 2011

Keywords

  • blood vessels
  • cell differentiation
  • cell migration
  • cysteine
  • endothelium
  • ischaemia
  • kinases
  • nitric oxide

ASJC Scopus subject areas

  • Pharmacology

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