Τόμος 27 (2009) – Τεύχος 1 – Άρθρο 27 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 27 (2009) – Issue 1– Article 27 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

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Hydrogen Sulphide Induces Angiogenesis

Ελληνικά – Greek

Άρθρο

Article

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Hydrogen sulphide (H2S) is emerging as an important signalling molecule in the cardiovascular and neuronal systems. Although H2S is known to relax vascular smooth muscle leading to a reduction in blood pressure, the role of this gaseous mediator in other aspects of the biology of vascular cells remains largely unexplored. In order to study the effects of H2S on neovascularisation, we have utilised an aqueous formulation of H2S. Incubation of endothelial cells (EC) with H2S enhanced their angiogenic potential as it promoted cell growth, migration and capillary morphogenesis on matrigel. In line with the in vitro observations, treatment of chicken chorioallantoic membranes (CAM) with H2S increased vascular length. Morever, exposure of EC to H2S resulted in increased phosphorylation of kinases linked to angiogenic responses, namely Akt, ERK and p38. Pretreatment of cells with the KATP channel blocker glibenclamide or the p38 inhibitor SB203580 abolished H2S-induced motility. Since glibenclamide inhibited H2S-triggered p38 phosphorylation, we propose that KATP channels lay upstream of p38. Once activated, p38 phosphorylates the actin-binding protein hsp27 to promote cell motility, as hsp27 silencing reduced H2S-driven migration. To determine whether endogenously produced H2S, similarly to exogensouly applied H2S drives the angiogenic response, CAMs were treated with PAG, an inhibitor of H2S biosynthesis; indeed, PAG-treated membranes displayed reduced vessel length and branching. Finally, pretreatment of cells with PAG or glibenclamide blocked vascular-endothelial growth factor-induced migration. In conclusion, we provide evidence that endogenously produced or exogenously administered H2S stimulates EC properties associated with angiogenesis through a KATP channel/MAPK pathway.