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
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
{"title":"内皮细胞在发育和成人血管生成过程中需要功能性FLVCR1a","authors":"Sara Petrillo,&nbsp;F. De Giorgio,&nbsp;F. Bertino,&nbsp;F. Garello,&nbsp;V. Bitonto,&nbsp;D. L. Longo,&nbsp;S. Mercurio,&nbsp;G. Ammirata,&nbsp;A. L. Allocco,&nbsp;V. Fiorito,&nbsp;D. Chiabrando,&nbsp;F. Altruda,&nbsp;E. Terreno,&nbsp;P. Provero,&nbsp;L. Munaron,&nbsp;T. Genova,&nbsp;A. Nóvoa,&nbsp;A. R. Carlos,&nbsp;S. Cardoso,&nbsp;M. Mallo,&nbsp;M. P. Soares,&nbsp;E. Tolosano","doi":"10.1007/s10456-023-09865-w","DOIUrl":null,"url":null,"abstract":"<div><p>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 <i>Flvcr1a</i> targeting in mice led to a reduced radial expansion of the retinal vasculature associated to decreased EC proliferation. Moreover, <i>Flvcr1a</i> 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 <i>Flvcr1a</i> 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.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 3","pages":"365 - 384"},"PeriodicalIF":9.2000,"publicationDate":"2023-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09865-w.pdf","citationCount":"3","resultStr":"{\"title\":\"Endothelial cells require functional FLVCR1a during developmental and adult angiogenesis\",\"authors\":\"Sara Petrillo,&nbsp;F. De Giorgio,&nbsp;F. Bertino,&nbsp;F. Garello,&nbsp;V. Bitonto,&nbsp;D. L. Longo,&nbsp;S. Mercurio,&nbsp;G. Ammirata,&nbsp;A. L. Allocco,&nbsp;V. Fiorito,&nbsp;D. Chiabrando,&nbsp;F. Altruda,&nbsp;E. Terreno,&nbsp;P. Provero,&nbsp;L. Munaron,&nbsp;T. Genova,&nbsp;A. Nóvoa,&nbsp;A. R. Carlos,&nbsp;S. Cardoso,&nbsp;M. Mallo,&nbsp;M. P. Soares,&nbsp;E. Tolosano\",\"doi\":\"10.1007/s10456-023-09865-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 <i>Flvcr1a</i> targeting in mice led to a reduced radial expansion of the retinal vasculature associated to decreased EC proliferation. Moreover, <i>Flvcr1a</i> 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 <i>Flvcr1a</i> 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.</p></div>\",\"PeriodicalId\":7886,\"journal\":{\"name\":\"Angiogenesis\",\"volume\":\"26 3\",\"pages\":\"365 - 384\"},\"PeriodicalIF\":9.2000,\"publicationDate\":\"2023-01-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s10456-023-09865-w.pdf\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Angiogenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10456-023-09865-w\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angiogenesis","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s10456-023-09865-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
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。

Endothelial cells require functional FLVCR1a during developmental and adult angiogenesis

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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信