{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:27:09Z","timestamp":1790839629298,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Estrogens exert beneficial effect on the blood vascular system. However, their role on the lymphatic system has been poorly investigated. We studied the protective effect of the 17\u03b2 estradiol\u2014the most potent endogenous estrogen\u2014in lymphedema\u2014a lymphatic dysfunction, which results in a massive fluid and fat accumulation in the limb.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Screening of DNA motifs able to mobilize ERs (estrogen receptors) and quantitative real-time polymerase chain reaction analysis revealed that estradiol promotes transcriptional activation of lymphangiogenesis-related gene expression including VEGF (vascular endothelial growth factor)-D, VEGFR (VEGF receptor)-3, lyve-1, and HASs (hyaluronan synthases). Using an original model of secondary lymphedema, we observed a protective effect of estradiol on lymphedema by reducing dermal backflow\u2014a representative feature of the pathology. Blocking ER\u03b1 by tamoxifen\u2014the selective estrogen modulator\u2014led to a remodeling of the lymphatic network associated with a strong lymphatic leakage. Moreover, the protection of lymphedema by estradiol treatment was abrogated by the endothelial deletion of the receptor ER\u03b1 in Tie2-Cre; ER\u03b1\n              <jats:sup>lox\/lox<\/jats:sup>\n              mice, which exhibit dilated lymphatic vessels. This remodeling correlated with a decrease in lymphangiogenic gene expression. In vitro, blocking ER\u03b1 by tamoxifen in lymphatic endothelial cells decreased cell\u2013cell junctions, inhibited migration and sprouting, and resulted in an inhibition of Erk but not of Akt phosphorylation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Estradiol protection from developing lymphedema is mediated by an activation of its receptor ER\u03b1 and is antagonized by tamoxifen. These findings reveal a new facet of the estrogen influence in the management of the lymphatic system and provide more evidence that secondary lymphedema is worsened by hormone therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.310997","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T09:05:22Z","timestamp":1523523922000},"page":"1346-1357","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":71,"title":["Lymphatic Vasculature Requires Estrogen Receptor-\u03b1 Signaling to Protect From Lymphedema"],"prefix":"10.1161","volume":"38","author":[{"given":"Florent","family":"Morfoisse","sequence":"first","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Tatin","sequence":"additional","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Chaput","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery (B.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Therville","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 1037-Centre de Recherche en Canc\u00e9rologie de Toulouse (N.T., J.G.-G.), Inserm, Universit\u00e9 Paul Sabatier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Vaysse","sequence":"additional","affiliation":[{"name":"Department of Gynecology Surgery, IUCT-Oncopole, Toulouse, France (C.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"M\u00e9tivier","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Centre National de la Recherche Scientifique 6290, Rennes, France (R.M.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Malloizel-Delaunay","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine (J.M.-D.), Centre Hospitalo-Universitaire Rangueil, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francoise","family":"Pujol","sequence":"additional","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Claire","family":"Godet","sequence":"additional","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"De Toni","sequence":"additional","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Boudou","sequence":"additional","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Grenier","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique, Laboratoire d\u2019analyse et d\u2019architecture des syst\u00e8mes, Toulouse, France (K.G., D.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dubuc","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique, Laboratoire d\u2019analyse et d\u2019architecture des syst\u00e8mes, Toulouse, France (K.G., D.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lacazette","sequence":"additional","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Catherine","family":"Prats","sequence":"additional","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Guillermet-Guibert","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 1037-Centre de Recherche en Canc\u00e9rologie de Toulouse (N.T., J.G.-G.), Inserm, Universit\u00e9 Paul Sabatier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francoise","family":"Lenfant","sequence":"additional","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Garmy-Susini","sequence":"additional","affiliation":[{"name":"From the Institute of Metabolic and Cardiovascular Diseases of Toulouse, Universit\u00e9 de Toulouse (F.M., F.T., F.P., A.C.G., F.D.T., F.B., E.L., A.C.P., F.L., B.G.-S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1500113"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2001-0045"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112062"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0390"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086185"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1986.tb04300.x"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.3.423"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2012.11.011"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.14.2905"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.4.8096"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513405200"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205692200"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(01)00179-9"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.2165\/11589180-000000000-00000"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00803.x"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03540400031027"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04480"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.3109\/09593980802667854"},{"key":"e_1_3_5_20_2","first-page":"206","article-title":"Primary lymphedema in children and adolescents: a follow-up study and review.","volume":"76","author":"Smeltzer DM","year":"1985","unstructured":"Smeltzer DM, Stickler GB, Schirger A. Primary lymphedema in children and adolescents: a follow-up study and review. Pediatrics. 1985;76:206\u2013218.","journal-title":"Pediatrics"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010815)92:4<748::AID-CNCR1378>3.0.CO;2-V"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1094"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199903000-00017"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-012-2828-y"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-015-3408-1"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2013.11.232"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2006.05.009"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221449198"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-495"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1177"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2013.05.005"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.175"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00598.2014"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.898445"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-3761"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71603"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220356"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.353151"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2006.4.83"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06184"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000127719.13255.81"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/200319121226"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207480"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.118.310997","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:19:58Z","timestamp":1715555998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.118.310997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1161\/ATVBAHA.118.310997"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.118.310997","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6]]},"assertion":[{"value":"2017-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}