Feline Leukemia Virus Subgroup C Receptor 1a (FLVCR1a) 是一种跨膜血红素导出蛋白，在胚胎血管发育中不可或缺。然而，在血管发育过程中，FLVCR1a 的确切作用仍未被完全定义。在这里，我们展示了与静止内皮细胞相比，FLVCR1a 在血管生成内皮细胞中高度表达。一致地，缺乏 FLVCR1a 的内皮细胞在多种发育和病理性血管生成模型中导致结构和功能异常的血管网络形成。首先，没有 FLVCR1a 的斑马鱼胚胎显示出有缺陷的间隔血管形成。此外，在小鼠中内皮细胞特异性靶向 FLVCR1a 导致视网膜血管周向扩张减少和内皮细胞增殖下降。而且，Flvcr1a 空缺的视网膜显示有缺陷的血管组织和外周细胞松散的连结。最后，在肿瘤血管生成的小鼠模型中，成年新生血管受到严重影响。缺乏 Flvcr1a 的肿瘤血管无组织地且功能紊乱。总的来说，我们的结果证明了 FLVCR1a 作为发育和病理性血管生成调节因子的关键作用，确定了 FLVCR1a 作为人类异常新生血管特征的潜在治疗靶标。 ©2023.作者（们）。

The Feline Leukemia Virus Subgroup C Receptor 1a (FLVCR1a) is a transmembrane heme exporter essential for embryonic vascular development. However, the exact role of FLVCR1a during blood vessel development remains largely undefined. Here, we show that FLVCR1a is highly expressed in angiogenic endothelial cells (ECs) compared to quiescent ECs. Consistently, ECs lacking FLVCR1a give rise to structurally and functionally abnormal vascular networks in multiple models of developmental and pathologic angiogenesis. Firstly, zebrafish embryos without FLVCR1a displayed defective intersegmental vessels formation. Furthermore, endothelial-specific Flvcr1a targeting in mice led to a reduced radial expansion of the retinal vasculature associated to decreased EC proliferation. Moreover, Flvcr1a null retinas showed defective vascular organization and loose attachment of pericytes. Finally, adult neo-angiogenesis is severely affected in murine models of tumor angiogenesis. Tumor blood vessels lacking Flvcr1a were disorganized and dysfunctional. Collectively, our results demonstrate the critical role of FLVCR1a as a regulator of developmental and pathological angiogenesis identifying FLVCR1a as a potential therapeutic target in human diseases characterized by aberrant neovascularization.© 2023. The Author(s).