Hypoxia-Inducible Factor-1.ALPHA. Is Involved in the Pro-angiogenic Effect of Hydrogen Sulfide under Hypoxic Stress

Abstract

Hydrogen sulfide (H2S) is known to have pro-angiogenic properties in mammals. In this study, we examined H2S played the role in pro-angiogenesis mediated by hypoxia-inducible factor (HIF)-1alpha under hypoxic conditions. Rat brain capillary endothelial cells (ECs) were treated with NaHS (a H2S donor) pretreated vascular smooth muscle cells (VSMCs) conditioned media. ECs proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ECs migration was assessed by chemotaxis chamber assay. Angiogenesis-associated gene expression levels were determined by reverse transcription-polymerase chain reaction (RT-PCR). HIF-1alpha and vascular endothelial growth factor (VEGF) accumulation was analyzed by Western blotting. HIF-1 binding activity was measured by electrophoretic mobility shift assay (EMSA). We found H2S induced both endothelial proliferation and migration in mimic hypoxic condition. In addition, H2S promoted VEGF and HIF-1alpha mRNA levels. H2S also significantly upregulated HIF-1alpha and VEGF protein levels and increased HIF-1alpha binding activity under hypoxic condition. Our findings suggest that HIF-1/VEGF is involved in H2S promotes proliferation and migration of ECs.