{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:59:20Z","timestamp":1791543560557,"version":"4.3.4"},"reference-count":146,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T00:00:00Z","timestamp":1602892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/15\/12\/31616"],"award-info":[{"award-number":["RG\/15\/12\/31616"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vascular endothelial growth factor receptors (VEGFRs) are part of the evolutionarily conserved VEGF signalling pathways that regulate the development and maintenance of the body\u2019s cardiovascular and lymphovascular systems. VEGFR3, encoded by the FLT4 gene, has an indispensable and well-characterized function in development and establishment of the lymphatic system. Autosomal dominant VEGFR3 mutations, that prevent the receptor functioning as a homodimer, cause one of the major forms of hereditary primary lymphoedema; Milroy disease. Recently, we and others have shown that FLT4 variants, distinct to those observed in Milroy disease cases, predispose individuals to Tetralogy of Fallot, the most common cyanotic congenital heart disease, demonstrating a novel function for VEGFR3 in early cardiac development. Here, we examine the familiar and emerging roles of VEGFR3 in the development of both lymphovascular and cardiovascular systems, respectively, compare how distinct genetic variants in FLT4 lead to two disparate human conditions, and highlight the research still required to fully understand this multifaceted receptor.<\/jats:p>","DOI":"10.1093\/cvr\/cvaa291","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T11:12:53Z","timestamp":1601896373000},"page":"1877-1890","source":"Crossref","is-referenced-by-count":67,"title":["The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3323-1337","authenticated-orcid":false,"given":"Richard M","family":"Monaghan","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-5997","authenticated-orcid":false,"given":"Donna J","family":"Page","sequence":"additional","affiliation":[{"name":"School of Healthcare Science, Manchester Metropolitan University, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-1356","authenticated-orcid":false,"given":"Pia","family":"Ostergaard","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard D","family":"Keavney","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, UK"},{"name":"Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,17]]},"reference":[{"key":"2021070715543597300_cvaa291-B1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1093\/cvr\/cvq062","article-title":"Microvascular fluid exchange and the revised starling principle","volume":"87","author":"Levick","year":"2010","journal-title":"Cardiovasc Res"},{"key":"2021070715543597300_cvaa291-B2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/cphy.c180015","article-title":"Lymphatic vessel network structure and physiology","volume":"9","author":"Breslin","year":"2018","journal-title":"Compr Physiol"},{"key":"2021070715543597300_cvaa291-B3","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.ijcard.2016.09.026","article-title":"The changing face of cardiovascular disease 2000-2012: an analysis of the world health organisation global health 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