{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:33:36Z","timestamp":1790393616217,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["SAF2013-43421-R"],"award-info":[{"award-number":["SAF2013-43421-R"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["SAF2013-45784-R"],"award-info":[{"award-number":["SAF2013-45784-R"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)","award":["ISCIII-CB06\/07\/0038"],"award-info":[{"award-number":["ISCIII-CB06\/07\/0038"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/00460"],"award-info":[{"award-number":["PI16\/00460"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01630"],"award-info":[{"award-number":["PI19\/01630"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003339","name":"Consejo Superior de Investigaciones Cient\u00edficas","doi-asserted-by":"publisher","award":["201920E022"],"award-info":[{"award-number":["201920E022"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Endoglin is a membrane glycoprotein primarily expressed by the vascular endothelium and involved in cardiovascular diseases. Upon the proteolytic processing of the membrane-bound protein, a circulating form of endoglin (soluble endoglin, sEng) can be released, and high levels of sEng have been observed in several endothelial-related pathological conditions, where it appears to contribute to endothelial dysfunction. Preeclampsia is a multisystem disorder of high prevalence in pregnant women characterized by the onset of high blood pressure and associated with increased levels of sEng. Although a pathogenic role for sEng involving hypertension has been reported in several animal models of preeclampsia, the exact molecular mechanisms implicated remain to be identified. To search for sEng-induced mediators of hypertension, we analyzed the protein secretome of human endothelial cells in the presence of sEng. We found that sEng induces the expression of BMP4 in endothelial cells, as evidenced by their proteomic signature, gene transcript levels, and BMP4 promoter activity. A mouse model of preeclampsia with high sEng plasma levels (sEng+) showed increased transcript levels of BMP4 in lungs, stomach, and duodenum, and increased circulating levels of BMP4, compared to those of control animals. In addition, after crossing female wild type with male sEng+ mice, hypertension appeared 18 days after mating, coinciding with the appearance of high plasma levels of BMP4. Also, serum levels of sEng and BMP4 were positively correlated in pregnant women with and without preeclampsia. Interestingly, sEng-induced arterial pressure elevation in sEng+ mice was abolished in the presence of the BMP4 inhibitor noggin, suggesting that BMP4 is a downstream mediator of sEng. These results provide a better understanding on the role of sEng in the physiopathology of preeclampsia and other cardiovascular diseases, where sEng levels are increased.<\/jats:p>","DOI":"10.3390\/cells9040988","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T13:01:39Z","timestamp":1587042099000},"page":"988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Potential Role of Circulating Endoglin in Hypertension via the Upregulated Expression of BMP4"],"prefix":"10.3390","volume":"9","author":[{"given":"Eunate","family":"Gallardo-Vara","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas Margarita Salas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, Spain"},{"name":"Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3556-2495","authenticated-orcid":false,"given":"Luis","family":"Gamella-Pozuelo","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas Margarita Salas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"},{"name":"Biomedical Research Institute of Salamanca (IBSAL) and Renal and Cardiovascular Physiopathology Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Perez-Roque","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Salamanca (IBSAL) and Renal and Cardiovascular Physiopathology Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Bartha","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Maternal and Fetal Medicine, University Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Garcia-Palmero","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas Margarita Salas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1085-2840","authenticated-orcid":false,"given":"J. Ignacio","family":"Casal","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas Margarita Salas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-7269","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"L\u00f3pez-Novoa","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Salamanca (IBSAL) and Renal and Cardiovascular Physiopathology Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0226-482X","authenticated-orcid":false,"given":"Miguel","family":"Pericacho","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Salamanca (IBSAL) and Renal and Cardiovascular Physiopathology Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1563-6162","authenticated-orcid":false,"given":"Carmelo","family":"Bernabeu","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas Margarita Salas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/nrm2262","article-title":"Extracellular control of TGFbeta signalling in vascular development and disease","volume":"8","author":"Arthur","year":"2007","journal-title":"Nat. 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