{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:32:55Z","timestamp":1790685175772,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["jidonline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Dermatology"],"published-print":{"date-parts":[[2017,9]]},"DOI":"10.1016\/j.jid.2017.04.033","type":"journal-article","created":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T03:02:05Z","timestamp":1494990125000},"page":"1995-2004","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":78,"title":["An Important Role of VEGF-C in Promoting Lymphedema Development"],"prefix":"10.1016","volume":"137","author":[{"given":"Epameinondas","family":"Gousopoulos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T.","family":"Proulx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia B.","family":"Bachmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar C.","family":"Dieterich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"Scholl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinem","family":"Karaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Detmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jid.2017.04.033_bib1","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1158\/0008-5472.CAN-12-4539","article-title":"VEGF-C and VEGF-D blockade inhibits inflammatory skin carcinogenesis","volume":"73","author":"Alitalo","year":"2013","journal-title":"Cancer Res"},{"key":"10.1016\/j.jid.2017.04.033_bib2","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1161\/CIRCRESAHA.109.197830","article-title":"Activated forms of VEGF-C and VEGF-D provide improved vascular function in skeletal muscle","volume":"104","author":"Anisimov","year":"2009","journal-title":"Circ Res"},{"key":"10.1016\/j.jid.2017.04.033_bib3","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/bjs.9766","article-title":"Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer","volume":"102","author":"Bains","year":"2015","journal-title":"Br J Surg"},{"key":"10.1016\/j.jid.2017.04.033_bib4","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1161\/01.RES.0000118600.91698.BB","article-title":"Comparative evaluation of FGF-2-, VEGF-A-, and VEGF-C-induced angiogenesis, lymphangiogenesis, vascular fenestrations, and permeability","volume":"94","author":"Cao","year":"2004","journal-title":"Circ Res"},{"key":"10.1016\/j.jid.2017.04.033_bib5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1089\/lrb.2016.0005","article-title":"Constitutively enhanced lymphatic pumping in the upper limbs of women who later develop breast cancer-related lymphedema","volume":"14","author":"Cintolesi","year":"2016","journal-title":"Lymphat Res Biol"},{"key":"10.1016\/j.jid.2017.04.033_bib6","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.1002\/cncr.25458","article-title":"Lymphedema beyond breast cancer: a systematic review and meta-analysis of cancer-related secondary lymphedema","volume":"116","author":"Cormier","year":"2010","journal-title":"Cancer"},{"key":"10.1016\/j.jid.2017.04.033_bib7","first-page":"185","article-title":"Serum level of VEGF-D in patients with primary lymphedema","volume":"37","author":"Fink","year":"2004","journal-title":"Lymphology"},{"key":"10.1016\/j.jid.2017.04.033_bib8","doi-asserted-by":"crossref","first-page":"34673","DOI":"10.1038\/srep34673","article-title":"High-resolution 3D volumetry versus conventional measuring techniques for the assessment of experimental lymphedema in the mouse hindlimb","volume":"6","author":"Frueh","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.jid.2017.04.033_bib9","doi-asserted-by":"crossref","first-page":"e89081","DOI":"10.1172\/jci.insight.89081","article-title":"Regulatory T-cell transfer ameliorates lymphedema and promotes lymphatic vessel function","volume":"1","author":"Gousopoulos","year":"2016","journal-title":"JCI Insight"},{"key":"10.1016\/j.jid.2017.04.033_bib10","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1016\/j.ajpath.2016.04.006","article-title":"Prominent lymphatic vessel hyperplasia with progressive dysfunction and distinct immune cell infiltration in lymphedema","volume":"186","author":"Gousopoulos","year":"2016","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jid.2017.04.033_bib11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/2045-824X-4-15","article-title":"Deciphering the roles of macrophages in developmental and inflammation stimulated lymphangiogenesis","volume":"4","author":"Harvey","year":"2012","journal-title":"Vasc Cell"},{"key":"10.1016\/j.jid.2017.04.033_bib12","doi-asserted-by":"crossref","first-page":"e12403","DOI":"10.14814\/phy2.12403","article-title":"Higher vascular endothelial growth factor-C concentration in plasma is associated with increased forearm capillary filtration capacity in breast cancer-related lymphedema","volume":"3","author":"Jensen","year":"2015","journal-title":"Physiol Rep"},{"key":"10.1016\/j.jid.2017.04.033_bib13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1089\/lrb.2009.0002","article-title":"Therapeutic responses to exogenous VEGF-C administration in experimental lymphedema: immunohistochemical and molecular characterization","volume":"7","author":"Jin da","year":"2009","journal-title":"Lymphat Res Biol"},{"key":"10.1016\/j.jid.2017.04.033_bib14","doi-asserted-by":"crossref","first-page":"6599","DOI":"10.1074\/jbc.273.12.6599","article-title":"A\u00a0recombinant mutant vascular endothelial growth factor-C that has lost vascular endothelial growth factor receptor-2 binding, activation, and vascular permeability activities","volume":"273","author":"Joukov","year":"1998","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jid.2017.04.033_bib15","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1161\/CIRCULATIONAHA.110.965384","article-title":"Growth factor therapy and autologous lymph node transfer in lymphedema","volume":"123","author":"Lahteenvuo","year":"2011","journal-title":"Circulation"},{"key":"10.1016\/j.jid.2017.04.033_bib16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nm.1960","article-title":"Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism","volume":"15","author":"Machnik","year":"2009","journal-title":"Nat Med"},{"key":"10.1016\/j.jid.2017.04.033_bib17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/84651","article-title":"Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3","volume":"7","author":"Makinen","year":"2001","journal-title":"Nat Med"},{"key":"10.1016\/j.jid.2017.04.033_bib18","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.jid.2015.12.001","article-title":"Excess lymphangiogenesis cooperatively induced by macrophages and CD4(+) T cells drives the pathogenesis of lymphedema","volume":"136","author":"Ogata","year":"2016","journal-title":"J\u00a0Invest Dermatol"},{"key":"10.1016\/j.jid.2017.04.033_bib19","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s10456-013-9332-2","article-title":"Non-invasive dynamic near-infrared imaging and quantification of vascular leakage in\u00a0vivo","volume":"16","author":"Proulx","year":"2013","journal-title":"Angiogenesis"},{"key":"10.1016\/j.jid.2017.04.033_bib20","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1016\/j.biomaterials.2013.03.034","article-title":"Use of a PEG-conjugated bright near-infrared dye for functional imaging of rerouting of tumor lymphatic drainage after sentinel lymph node metastasis","volume":"34","author":"Proulx","year":"2013","journal-title":"Biomaterials"},{"key":"10.1016\/j.jid.2017.04.033_bib21","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1161\/01.RES.0000073584.46059.E3","article-title":"VEGF-D is the strongest angiogenic and lymphangiogenic effector among VEGFs delivered into skeletal muscle via adenoviruses","volume":"92","author":"Rissanen","year":"2003","journal-title":"Circ Res"},{"key":"10.1016\/j.jid.2017.04.033_bib22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s11936-000-0018-x","article-title":"Lymphedema","volume":"2","author":"Rockson","year":"2000","journal-title":"Curr Treat Options Cardiovasc Med"},{"key":"10.1016\/j.jid.2017.04.033_bib23","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1089\/lrb.2008.6201","article-title":"Secondary lymphedema: is it a primary disease?","volume":"6","author":"Rockson","year":"2008","journal-title":"Lymphat Res Biol"},{"key":"10.1016\/j.jid.2017.04.033_bib24","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1196\/annals.1413.014","article-title":"Estimating the population burden of lymphedema","volume":"1131","author":"Rockson","year":"2008","journal-title":"Ann NY Acad Sci"},{"key":"10.1016\/j.jid.2017.04.033_bib25","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.mvr.2006.05.009","article-title":"Secondary lymphedema in the mouse tail: Lymphatic hyperplasia, VEGF-C upregulation, and the protective role of MMP-9","volume":"72","author":"Rutkowski","year":"2006","journal-title":"Microvasc Res"},{"key":"10.1016\/j.jid.2017.04.033_bib26","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1096\/fj.01-1042com","article-title":"Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes","volume":"16","author":"Saaristo","year":"2002","journal-title":"FASEB J"},{"key":"10.1016\/j.jid.2017.04.033_bib27","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1084\/jem.20020587","article-title":"Lymphangiogenic gene therapy with minimal blood vascular side effects","volume":"196","author":"Saaristo","year":"2002","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.jid.2017.04.033_bib28","doi-asserted-by":"crossref","first-page":"32127","DOI":"10.1074\/jbc.274.45.32127","article-title":"Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers","volume":"274","author":"Stacker","year":"1999","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jid.2017.04.033_bib29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/lrb.2008.1026","article-title":"Recent advances in breast cancer-related lymphedema of the arm: lymphatic pump failure and predisposing factors","volume":"7","author":"Stanton","year":"2009","journal-title":"Lymphat Res Biol"},{"key":"10.1016\/j.jid.2017.04.033_bib30","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1053\/j.gastro.2015.03.005","article-title":"Vascular endothelial growth factor C disrupts the endothelial lymphatic barrier to promote colorectal cancer invasion","volume":"148","author":"Tacconi","year":"2015","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jid.2017.04.033_bib31","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.tcb.2005.06.004","article-title":"Molecular lymphangiogenesis: new players","volume":"15","author":"Tammela","year":"2005","journal-title":"Trends Cell Biol"},{"key":"10.1016\/j.jid.2017.04.033_bib32","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/nm1689","article-title":"Therapeutic differentiation and maturation of lymphatic vessels after lymph node dissection and transplantation","volume":"13","author":"Tammela","year":"2007","journal-title":"Nat Med"},{"key":"10.1016\/j.jid.2017.04.033_bib33","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s10456-015-9469-2","article-title":"VEGF-C and VEGF-C156S in the pro-lymphangiogenic growth factor therapy of lymphedema: a large animal study","volume":"18","author":"Visuri","year":"2015","journal-title":"Angiogenesis"},{"key":"10.1016\/j.jid.2017.04.033_bib34","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/01.sap.0000257149.42922.7e","article-title":"Lymphedema: a comprehensive review","volume":"59","author":"Warren","year":"2007","journal-title":"Ann Plast Surg"},{"key":"10.1016\/j.jid.2017.04.033_bib35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0002-9440(10)65582-4","article-title":"Vascular endothelial growth factor-C (VEGF-C\/VEGF-2) promotes angiogenesis in the setting of tissue ischemia","volume":"153","author":"Witzenbichler","year":"1998","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jid.2017.04.033_bib36","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1172\/JCI15830","article-title":"VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema","volume":"111","author":"Yoon","year":"2003","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jid.2017.04.033_bib37","doi-asserted-by":"crossref","first-page":"C392","DOI":"10.1152\/ajpcell.00306.2011","article-title":"Lymphatic function is regulated by a coordinated expression of lymphangiogenic and anti-lymphangiogenic cytokines","volume":"302","author":"Zampell","year":"2012","journal-title":"Am J Physiol Cell Physiol"},{"issue":"11","key":"10.1016\/j.jid.2017.04.033_bib38","doi-asserted-by":"crossref","first-page":"e49940","DOI":"10.1371\/journal.pone.0049940","article-title":"CD4(+) cells regulate fibrosis and lymphangiogenesis in response to lymphatic fluid stasis","volume":"7","author":"Zampell","year":"2012","journal-title":"PloS One"}],"container-title":["Journal of Investigative Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022202X17315348?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022202X17315348?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,11,23]],"date-time":"2018-11-23T08:55:04Z","timestamp":1542963304000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022202X17315348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["S0022202X17315348"],"URL":"https:\/\/doi.org\/10.1016\/j.jid.2017.04.033","relation":{},"ISSN":["0022-202X"],"issn-type":[{"value":"0022-202X","type":"print"}],"subject":[],"published":{"date-parts":[[2017,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"An Important Role of VEGF-C in Promoting Lymphedema Development","name":"articletitle","label":"Article Title"},{"value":"Journal of Investigative Dermatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jid.2017.04.033","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.","name":"copyright","label":"Copyright"}]}}