Regulation and role of endogenously produced hydrogen sulfide in angiogenesis

Abstract

Recent studies have implicated endogenously produced H2S in the angiogenic process. On one hand, pharmacological inhibition and silencing of the enzymes involved in H2S synthesis attenuate the angiogenic properties of endothelial cells, including proliferation, migration and tube-like structure network formation. On the other hand, enhanced production of H2S by substrate supplementation or over-expression of H2S-producing enzymes leads to enhanced angiogenic responses in cultured endothelial cells. Importantly, H2S up-regulates expression of the key angiogenic factor vascular endothelial growth factor (VEGF) and contributes to the angiogenic signaling in response to VEGF. The signaling pathways mediating H2S-induced angiogenesis include mitogen-activated protein kinases, phosphoinositide-3 kinase, nitric oxide/cGMP-regulated cascades and ATP-sensitive potassium channels. Endogenously produced H2S has also been shown to facilitate neovascularization in prototypical model systems in vivo, and to contribute to wound healing, post-ischemic angiogenesis in the heart and other tissues, as well as in tumor angiogenesis. Targeting of H2S synthesizing enzymes might offer novel therapeutic opportunities for angiogenesis-related diseases.

Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement

“…Our present study also found that NaHS significantly enhanced the numbers of branching points to promote tube formation of HUVECs. One previous study found that H 2 S upregulated expression of VEGF and contributed to the angiogenic signalling in response to VEGF . VEGF represented a growth factor with important pro‐angiogenic activity, having a mitogenic and an anti‐apoptotic effect on endothelial cells, increasing the vascular permeability, promoting cell migration, etc .…”

“…H 2 S also increased the stability and transcriptional activity of specificity protein 1 to enhance VEGFR2 transcription. Moreover, enhanced VEGF increased binding with VEGFR2 to promote H 2 S production presumably via CSE activating in a calcium‐dependent manner . Taken together, the enhanced VEGF and H 2 S levels possibly generate a benign feedback to strengthen each other in the wound healing.…”

Sulphurous Mineral Waters: New Applications for Health

“…New microvessel formation or angiogenesis occurs as a consequence of these mechanisms and we propose that H 2 S absorbed through the skin can potentiate this effect [39] (Figure 2). …”

Mast cell concentration and skin wound contraction in rats treated with Ximenia americana L

“…During the fibroplasia period there is a migration and proliferation of fibroblasts at the site of injury, as well as intensive production of collagen, fibronectin and glycosaminoglycans, which contribute to the formation of granulation tissue; some fibroblasts acquire actin and myosin myofilaments, which perform wound contraction 23 . Collagen production is continuous and growing until about the 21st postoperative, when establishing homeostasis and the degradation rate is balanced with the synthesis 24 . Since angiogenesis is a physiological process that refers to the production of new blood vessels from preexisting, both on growth and development, as well as wound healing and chronic inflammations 24 .…”

“…Collagen production is continuous and growing until about the 21st postoperative, when establishing homeostasis and the degradation rate is balanced with the synthesis 24 . Since angiogenesis is a physiological process that refers to the production of new blood vessels from preexisting, both on growth and development, as well as wound healing and chronic inflammations 24 . On slides stained with Masson's Trichrome, it was observed high concentrations of collagen fibers in all groups.…”