In vascular endothelium H2S acts as vasorelaxant, anti-inflammatory and proangiogenic factor. Here we show the effects of H2S in vascular physiopathology considering tumor vascularization and the possible protective role in heart injury and endothelial cell dysfunction. Although the underlying mechanisms are still partially unclear, calcium handling plays a pivotal role in the mediation of H2S biological effects. Here we investigate the calcium signals induced by H2S administration in different cardiovascular cell types including a pathological model. Ca2+ imaging experiments reveal that NaHS, a H2S donor, activates Ca2+ signals both in normal endothelial cells (HMECs) as well as tumor- derived endothelial cells (BTECs)with differences in peak amplitude and sensitivity. While NaHS fails to promote either migration and proliferation on HMECs, BTEC migration was enhanced at low concentrations. Interestingly cystathionine γ-lyase inhibitor (a H2S producing enzyme) reduces the percentage of VEGF-responding cells,and inhibits BTEC migration. In the second part of the research we evaluated the protective role of H2S on heart injury and EC dysfunction by the use of a rat cardiomyoblast cell line (H9C2) and of HMECs. The protective role of NaHS for oxidative stress and myocardial injury was studied preconditioning HMECs and H9C2 with NaHS followed by ￼￼H2O2 incubation or hypoxic assay. In both experiments H2S protects cells from death. Moreover H2S decreases Ca2+ levels in resting H9C2: this effect is mimicked by nifedipine, a L-type Ca2+ channel inhibitor.Interestingly nifedipine preconditioning protects H9C2 from H2O2. These data suggest an important role of H2S as a proangiogenic and protective agent:its activities on different districts of cardiovascular system could be mediated by direct or indirect regulation of specific calcium channels in pathophysiological conditions.
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