Background Hydrogen sulphide (H2S) is considered as the third member of the gasotransmitter family, along with nitric oxide (NO) and carbon monoxide. H2S 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 H2S in muscle angiogenesis. However, the importance of endogenous H2S for brain angiogenesis during development remains unknown. We therefore aimed at determining the role of H2S in brain vascular development. Methods and results Both knockdown and knockout of H2S-producing enzymes, cystathionine β-synthase ( cbs ) and cystathionine γ-lyase ( cth ), 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 H2S donor GYY4137 alleviated the defects of brain vascular development in cbs and cth morphants. Quantitative analysis of the midbrain vascular network showed that H2S enhances angiogenesis without affecting the topological structure of the brain vasculature. Mechanically, nitric oxide synthase 2a ( nos2a ) expression and NO production were decreased in both cbs and cth morphants. Overexpression of nos2a by coinjection of cbs or cth MO with full-length zebrafish nos2a mRNA alleviated the brain vascular developmental defects in cbs and cth morphants. Conclusion We conclude that H2S promotes brain developmental angiogenesis via the NOS/NO pathway in zebrafish. All data relevant to the study are included in the article or uploaded as supplementary information. No additional unpublished data are available.

中文翻译：

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H2S 通过斑马鱼的 NOS/NO 通路促进发育性脑血管生成

背景 硫化氢 (H2S) 与一氧化氮 (NO) 和一氧化碳一起被认为是气体递质家族的第三个成员。据报道，H2S 通过促进内皮细胞的生长、迁移和管状结构形成来诱导血管生成。这些研究是在细胞培养、小鼠基质胶塞测定模型、大鼠伤口愈合模型或大鼠后肢缺血模型的条件下进行的。最近的体内研究表明 H2S 在肌肉血管生成中的生理重要性。然而，内源性 H2S 在发育过程中对脑血管生成的重要性仍然未知。因此，我们旨在确定 H2S 在脑血管发育中的作用。方法和结果 抑制和敲除产生 H2S 的酶，胱硫醚 β-合酶 (cbs) 和胱硫醚 γ-裂解酶 (cth)，使用吗啉代寡核苷酸和成簇的定期间隔的短回文重复序列/Cas9 介导的突变，损害了斑马鱼幼虫的脑血管发育。与缓释 H2S 供体 GYY4137 孵育缓解了 cbs 和 cth morphant 脑血管发育的缺陷。中脑血管网络的定量分析表明，H2S 增强血管生成而不影响脑血管系统的拓扑结构。机械地，一氧化氮合酶 2a (nos2a) 的表达和 NO 的产生在 cbs 和 cth morphant 中都降低了。通过将 cbs​​ 或 cth MO 与全长斑马鱼 nos2a mRNA 共注射过表达 nos2a 可减轻 cbs 和 cth morphants 的脑血管发育缺陷。结论 我们得出结论，H2S 通过 NOS/NO 通路促进斑马鱼的脑发育血管生成。所有与研究相关的数据都包含在文章中或作为补充信息上传。没有其他未发表的数据可用。