内皮细胞在发育和成人血管生成过程中需要功能性FLVCR1a

IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Angiogenesis Pub Date : 2023-01-11 DOI:10.1007/s10456-023-09865-w
Sara Petrillo, F. De Giorgio, F. Bertino, F. Garello, V. Bitonto, D. L. Longo, S. Mercurio, G. Ammirata, A. L. Allocco, V. Fiorito, D. Chiabrando, F. Altruda, E. Terreno, P. Provero, L. Munaron, T. Genova, A. Nóvoa, A. R. Carlos, S. Cardoso, M. Mallo, M. P. Soares, E. Tolosano
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引用次数: 3

摘要

猫白血病病毒C亚群受体1a(FLVCR1a)是胚胎血管发育所必需的跨膜血红素输出物。然而,FLVCR1a在血管发育过程中的确切作用在很大程度上仍不明确。在这里,我们发现与静止的内皮细胞相比,FLVCR1a在血管生成内皮细胞中高度表达。一贯地,在多种发育和病理血管生成模型中,缺乏FLVCR1a的内皮细胞会导致结构和功能异常的血管网络。首先,没有FLVCR1a的斑马鱼胚胎显示出节间血管形成缺陷。此外,内皮特异性Flvcr1a靶向小鼠导致视网膜血管系统的径向扩张减少,这与EC增殖减少有关。此外,Flvcr1a缺失的视网膜显示出血管组织缺陷和周细胞附着疏松。最后,成年新生血管生成在肿瘤血管生成的小鼠模型中受到严重影响。缺乏Flvcr1a的肿瘤血管紊乱且功能紊乱。总之,我们的研究结果证明了FLVCR1a作为发育和病理性血管生成的调节因子的关键作用,确定了FLVCR1a是以异常血管生成为特征的人类疾病的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Endothelial cells require functional FLVCR1a during developmental and adult angiogenesis

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.

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来源期刊
Angiogenesis
Angiogenesis PERIPHERAL VASCULAR DISEASE-
CiteScore
21.90
自引率
8.20%
发文量
37
审稿时长
6-12 weeks
期刊介绍: Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.
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