Angiogenesis is a precise process mediated by a variety of signals and the environmental niche. Although the essential trace element zinc and its homeostasis are essential for maintaining proper cellular functions, whether zinc plays a role in angiogenesis is currently unknown. Using zebrafish embryos as a model system, we found that zinc treatment significantly increased the expression of the slc39a5 gene, which encodes the zinc transporter Slc39a5. Moreover, knocking down slc39a5 expression using either a morpholino or CRISPR/Cas9-mediated gene editing led to cardiac ischaemia and an accumulation of red blood cells in the caudal vein plexus (CVP), as well as delayed venous sprouting and fewer vascular loops in the CVP region during early development. Further analysis revealed significantly reduced proliferation and delayed cell migration in the caudal vein of slc39a5 morphants. At the mechanistic level, we found increased levels of systemic zinc in slc39a5-deficient embryos, and chelating zinc restored CVP development. In addition, we found that zinc overload in wild-type embryos leads to impaired CVP formation. Taken together, these results indicate that Slc39a5 plays a critical role in endothelial sprouting and migration in venous angiogenesis by regulating zinc homeostasis.

血管生成是由各种信号和环境生态位介导的精确过程。尽管必需的微量元素锌及其体内平衡对于维持适当的细胞功能至关重要，但锌是否在血管生成中起作用目前尚不清楚。使用斑马鱼胚胎作为模型系统，我们发现锌处理显着增加了slc39a5基因的表达，该基因编码锌转运蛋白 Slc39a5。此外，击倒slc39a5使用吗啉或 CRISPR/Cas9 介导的基因编辑进行表达导致心脏缺血和尾静脉丛 (CVP) 中红细胞的积累，以及早期发育过程中 CVP 区域的静脉萌发延迟和血管袢减少. 进一步的分析显示slc39a5 morphant尾静脉的增殖显着减少和细胞迁移延迟。在机制水平上，我们发现slc39a5中全身锌的水平增加- 缺陷胚胎和螯合锌恢复 CVP 发育。此外，我们发现野生型胚胎中的锌过载会导致 CVP 形成受损。总之，这些结果表明 Slc39a5 通过调节锌稳态在静脉血管生成中的内皮萌发和迁移中起关键作用。