血管生成的分子机制已经被广泛地研究，但仍有许多控制内皮细胞行为和命运的基因需要描述。在这里，我们表征了Apold1（载脂蛋白L域包含1）在体内和体外血管生成中的作用。单个细胞分析揭示，跨组织表达Apold1的表达仅限于血管系统，内皮细胞中Apold1的表达对环境因素高度敏感。使用Apold1-/-小鼠，我们发现Apold1在发育中是可有可无的，并不影响后天视网膜血管生成，也不改变成年人的脑和肌肉血管网络。然而，在照光性中风和股动脉结扎后暴露于缺血条件下时，Apold1-/-小鼠显示出明显的恢复和再血管化障碍。我们还发现，人类肿瘤内皮细胞表达Apold1的水平显著较高，Apold1在小鼠体内的缺失抑制了皮下B16黑色素瘤的生长，导致其血管较小且灌注不良。机械上，细胞生长因子刺激和缺氧可以激活ECs中的Apold1，并内在地控制ECs的增殖而不是迁移。我们的数据表明Apold1是病理情况下血管生成的关键调节因子，而它不影响发育性血管生成，因此成为临床研究的有希望候选物品。©2023年作者。

The molecular mechanisms of angiogenesis have been intensely studied, but many genes that control endothelial behavior and fate still need to be described. Here, we characterize the role of Apold1 (Apolipoprotein L domain containing 1) in angiogenesis in vivo and in vitro. Single-cell analyses reveal that - across tissues - the expression of Apold1 is restricted to the vasculature and that Apold1 expression in endothelial cells (ECs) is highly sensitive to environmental factors. Using Apold1-/- mice, we find that Apold1 is dispensable for development and does not affect postnatal retinal angiogenesis nor alters the vascular network in adult brain and muscle. However, when exposed to ischemic conditions following photothrombotic stroke as well as femoral artery ligation, Apold1-/- mice display dramatic impairments in recovery and revascularization. We also find that human tumor endothelial cells express strikingly higher levels of Apold1 and that Apold1 deletion in mice stunts the growth of subcutaneous B16 melanoma tumors, which have smaller and poorly perfused vessels. Mechanistically, Apold1 is activated in ECs upon growth factor stimulation as well as in hypoxia, and Apold1 intrinsically controls EC proliferation but not migration. Our data demonstrate that Apold1 is a key regulator of angiogenesis in pathological settings, whereas it does not affect developmental angiogenesis, thus making it a promising candidate for clinical investigation.© 2023. The Author(s).