HS promotes developmental brain angiogenesis via the NOS/NO pathway in zebrafish.

BACKGROUND

Hydrogen sulphide (HS) is considered as the third member of the gasotransmitter family, along with nitric oxide (NO) and carbon monoxide. HS has been reported to induce angiogenesis by promoting the growth, migration and tube-like structure formation of endothelial cells. Those studies were conducted in conditions of cell culture, mouse Matrigel plug assay model, rat wound healing model or rat hindlimb ischaemia model. Recent in vivo studies showed the physiological importance of HS in muscle angiogenesis. However, the importance of endogenous HS for brain angiogenesis during development remains unknown. We therefore aimed at determining the role of HS in brain vascular development.

METHODS AND RESULTS

Both knockdown and knockout of HS-producing enzymes, cystathionine β-synthase () and cystathionine γ-lyase (), using morpholino oligonucleotides and clustered regularly interspaced short palindromic repeats/Cas9-mediated mutation, impaired brain vascular development of larval zebrafish. Incubation with the slow-releasing HS donor GYY4137 alleviated the defects of brain vascular development in and morphants. Quantitative analysis of the midbrain vascular network showed that HS enhances angiogenesis without affecting the topological structure of the brain vasculature. Mechanically, nitric oxide synthase 2a () expression and NO production were decreased in both and morphants. Overexpression of by coinjection of or MO with full-length zebrafish nos2a mRNA alleviated the brain vascular developmental defects in and morphants.

CONCLUSION

We conclude that HS promotes brain developmental angiogenesis via the NOS/NO pathway in zebrafish.