{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:49:21Z","timestamp":1790660961896,"version":"4.1.0"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>VEGFA (Vascular endothelial growth factor A) and its receptor VEGFR2 (vascular endothelial growth factor receptor 2) drive angiogenesis in several pathologies, including diabetic retinopathy, wet age-related macular degeneration, and cancer. Studies suggest roles for HSPGs (heparan sulfate proteoglycans) in this process, although the nature of this involvement remains elusive. Here, we set to establish the role of the HSPG SDC4 (syndecan-4) in pathological angiogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>We report that angiogenesis is impaired in mice null for SDC4 in models of neovascular eye disease and tumor development. Our work demonstrates that SDC4 is the only SDC whose gene expression is upregulated during pathological angiogenesis and is selectively enriched on immature vessels in retinas from diabetic retinopathy patients. Combining in vivo and tissue culture models, we identified SDC4 as a downstream mediator of functional angiogenic responses to VEGFA. We found that SDC4 resides at endothelial cell junctions, interacts with vascular endothelial cadherin, and is required for its internalization in response to VEGFA. Finally, we show that pathological angiogenic responses are inhibited in a model of wet age-related macular degeneration by targeting SDC4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We show that SDC4 is a downstream mediator of VEGFA-induced vascular endothelial cadherin internalization during pathological angiogenesis and a potential target for antiangiogenic therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.121.315941","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T06:12:34Z","timestamp":1613628754000},"page":"1374-1389","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Pathological Angiogenesis Requires Syndecan-4 for Efficient VEGFA-Induced VE-Cadherin Internalization"],"prefix":"10.1161","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6163-4590","authenticated-orcid":true,"given":"Giulia","family":"De Rossi","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (G.D.R., S.A., J.R.W.)."},{"name":"Department of Cell Biology (G.D.R.), UCL Institute of Ophthalmology, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"V\u00e4h\u00e4tupa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University, Finland (M.V., U.M., L.P., H.U.-J., T.A.H.J.)."},{"name":"Departments of Orthopedics and Traumatology and Tampere Eye Centre, Tampere University Hospital, Finland (M.V., U.M., L.P., H.U.-J., T.A.H.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Cristante","sequence":"additional","affiliation":[{"name":"Genetics Department (E.C., S.E.L., J.W.B.), UCL Institute of Ophthalmology, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Arokiasamy","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (G.D.R., S.A., J.R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidath E.","family":"Liyanage","sequence":"additional","affiliation":[{"name":"Genetics Department (E.C., S.E.L., J.W.B.), UCL Institute of Ophthalmology, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"May","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University, Finland (M.V., U.M., L.P., H.U.-J., T.A.H.J.)."},{"name":"Departments of Orthopedics and Traumatology and Tampere Eye Centre, Tampere University Hospital, Finland (M.V., U.M., L.P., H.U.-J., T.A.H.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pellinen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University, Finland (M.V., U.M., L.P., H.U.-J., T.A.H.J.)."},{"name":"Departments of Orthopedics and Traumatology and Tampere Eye Centre, Tampere University Hospital, Finland (M.V., U.M., L.P., H.U.-J., T.A.H.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannele","family":"Uusitalo-J\u00e4rvinen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University, Finland (M.V., U.M., L.P., H.U.-J., T.A.H.J.)."},{"name":"Departments of Orthopedics and Traumatology and Tampere Eye Centre, Tampere University Hospital, Finland 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