Role of hydrogen sulphide in physiological and pathological angiogenesis.

The role of hydrogen sulphide (H 2 S) in angiogenesis has been widely demonstrated. Vascular endothelial growth factor (VEGF) plays an important role in H 2 S-induced angiogenesis. H 2 S promotes angiogenesis by upregulating VEGF via pro-angiogenic signal transduction. The involved signalling pathways include the mitogen-activated protein kinase pathway, phosphoinositide-3 kinase pathway, nitric oxide (NO) synthase/NO pathway, signal transducer and activator of transcription 3 (STAT3) pathway, and adenosine triphosphate (ATP)-sensitive potassium (K ATP ) channels. H 2 S has been shown to contribute to tumour angiogenesis, diabetic wound healing, angiogenesis in cardiac and cerebral ischaemic tissues, and physiological angiogenesis during the menstrual cycle and pregnancy. Furthermore, H 2 S can exert an anti-angiogenic effect by inactivating Wnt/β-catenin signalling or blocking the STAT3 pathway in tumours. Therefore, H 2 S plays a double-edged sword role in the process of angiogenesis. The regulation of H 2 S production is a promising therapeutic approach for angiogenesis-associated diseases. Novel H 2 S donors and/or inhibitors can be developed in the treatment of angiogenesis-dependent diseases.