Hydrogen sulphide triggers VEGF-induced intracellular Ca2+ signals in human endothelial cells but not in their immature progenitors

Duilio Michele Potenza, Germano Guerra, Daniele Avanzato, Valentina Poletto, Sumedha Pareek, Daniele Guido, Angelo Gallanti, Vittorio Rosti, Luca Munaron, Franco Tanzi, Francesco Moccia

Research output: Contribution to journalArticlepeer-review

Abstract

Hydrogen sulphide (H2S) is a newly discovered gasotransmitter that regulates multiple steps in VEGF-induced angiogenesis. An increase in intracellular Ca2+ concentration ([Ca2+]i) is central to endothelial proliferation and may be triggered by both VEGF and H2S. Albeit VEGFR-2 might serve as H2S receptor, the mechanistic relationship between VEGF- and H2S-induced Ca2+ signals in endothelial cells is unclear. The present study aimed at assessing whether and how NaHS, a widely employed H2S donor, stimulates pro-angiogenic Ca2+ signals in Ea.hy926 cells, a suitable surrogate for mature endothelial cells, and human endothelial progenitor cells (EPCs). We found that NaHS induced a dose-dependent increase in [Ca2+]i in Ea.hy926 cells. NaHS-induced Ca2+ signals in Ea.hy926 cells did not require extracellular Ca2+ entry, while they were inhibited upon pharmacological blockade of the phospholipase C/inositol-1,4,5-trisphosphate (InsP3) signalling pathway. Moreover, the Ca2+ response to NaHS was prevented by genistein, but not by SU5416, which selectively inhibits VEGFR-2. However, VEGF-induced Ca2+ signals were suppressed by dl-propargylglycine (PAG), which blocks the H2S-producing enzyme, cystathionine γ-lyase. Consistent with these data, VEGF-induced proliferation and migration were inhibited by PAG in Ea.hy926 cells, albeit NaHS alone did not influence these processes. Conversely, NaHS elevated [Ca2+]i only in a modest fraction of circulating EPCs, whereas neither VEGF-induced Ca2+ oscillations nor VEGF-dependent proliferation were affected by PAG. Therefore, H2S-evoked elevation in [Ca2+]i is essential to trigger the pro-angiogenic Ca2+ response to VEGF in mature endothelial cells, but not in their immature progenitors.

Original languageEnglish
Pages (from-to)225-234
Number of pages10
JournalCell Calcium
Volume56
Issue number3
DOIs
Publication statusPublished - 2014

Keywords

  • Ca release
  • Dl-Propargylglycine
  • Endothelial progenitor cells
  • HUVECs
  • Hydrogen sulphide
  • Proliferation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology
  • Medicine(all)

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