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, 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","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":null,"pages":null},"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, 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\",\"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\":null,\"pages\":null},\"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}
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.
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.