{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:28:28Z","timestamp":1790843308576,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["SAF2013-43421-R to CB; SAF2017-83785-R and SAF2014-23801 to ALC"],"award-info":[{"award-number":["SAF2013-43421-R to CB; SAF2017-83785-R and SAF2014-23801 to ALC"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003339","name":"Consejo Superior de Investigaciones Cient\u00edficas","doi-asserted-by":"publisher","award":["201920E022 to CB"],"award-info":[{"award-number":["201920E022 to CB"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)","award":["ISCIII-CB06\/07\/0038 to CB"],"award-info":[{"award-number":["ISCIII-CB06\/07\/0038 to CB"]}]},{"name":"Czech Republic Specific University Research","award":["SVV-260414 to PN"],"award-info":[{"award-number":["SVV-260414 to PN"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Upon inflammation, monocyte-derived macrophages (M\u03a6) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-M\u03a6) and a good resolution (M-M\u03a6) of the inflammatory process. The functional activity of polarized M\u03a6 is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and M\u03a6 that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the M\u03a6 secretome involved in the shedding of soluble endoglin. We find that the GM-M\u03a6 secretome contains metalloprotease 12 (MMP-12), a GM-M\u03a6 specific marker that may account for the anti-angiogenic activity of the GM-M\u03a6 secretome. Cell surface endoglin is present in both GM-M\u03a6 and M-M\u03a6, but soluble endoglin is only detected in GM-M\u03a6 culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both M\u03a6 and endothelial cells. These data demonstrate a direct correlation between GM-M\u03a6 polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.<\/jats:p>","DOI":"10.3390\/ijms20123107","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T10:52:31Z","timestamp":1561459951000},"page":"3107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells"],"prefix":"10.3390","volume":"20","author":[{"given":"Mikel","family":"Aristorena","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, 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"}]},{"given":"Eunate","family":"Gallardo-Vara","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7568-6989","authenticated-orcid":false,"given":"Matej","family":"Vicen","sequence":"additional","affiliation":[{"name":"Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, 500 05 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateo","family":"de Las Casas-Engel","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Ojeda-Fernandez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, 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"}]},{"given":"Concepci\u00f3n","family":"Nieto","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Blanco","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, 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"}]},{"given":"Ana C.","family":"Valbuena-Diez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, 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"}]},{"given":"Luisa M.","family":"Botella","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9568-7295","authenticated-orcid":false,"given":"Petr","family":"Nachtigal","sequence":"additional","affiliation":[{"name":"Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, 500 05 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel L.","family":"Corbi","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4114-277X","authenticated-orcid":false,"given":"Mar\u00eda","family":"Colmenares","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Bernabeu","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, 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":[[2019,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nri2448","article-title":"Exploring the full spectrum of macrophage activation","volume":"8","author":"Mosser","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3109\/08916934.2015.1027815","article-title":"Macrophages in vascular inflammation-From atherosclerosis to vasculitis","volume":"48","author":"Shirai","year":"2015","journal-title":"Autoimmunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1161\/CIRCRESAHA.117.311071","article-title":"Resident and monocyte-derived macrophages in cardiovascular disease","volume":"122","author":"Honold","year":"2018","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/j.jacc.2018.08.2147","article-title":"Macrophage trafficking, inflammatory resolution, and genomics in atherosclerosis: JACC macrophage in CVD series (Part 2)","volume":"72","author":"Moore","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1172\/JCI93025","article-title":"CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis","volume":"128","author":"Guo","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3389\/fcvm.2018.00097","article-title":"Dynamic macrophages: Understanding mechanisms of activation as guide to therapy for atherosclerotic vascular disease","volume":"5","author":"Decano","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3389\/fphys.2012.00128","article-title":"Vascular inflammatory cells in hypertension","volume":"3","author":"Harrison","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e007849","DOI":"10.1161\/JAHA.117.007849","article-title":"Role of monocytes in heart failure and atrial fibrillation","volume":"7","author":"Shahid","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jacc.2013.09.019","article-title":"The role of monocytes in angiogenesis and atherosclerosis","volume":"63","author":"Jaipersad","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/cvr\/cvv147","article-title":"Monocyte trafficking across the vessel wall","volume":"107","author":"Gerhardt","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.3389\/fimmu.2018.02650","article-title":"Distinct migratory properties of M1, M2, and resident macrophages are regulated by \u03b1D\u03b22 and \u03b1M\u03b22 integrin-mediated adhesion","volume":"9","author":"Cui","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1182\/blood-2012-06-435347","article-title":"Endothelial endoglin is involved in inflammation: Role in leukocyte adhesion and transmigration","volume":"121","author":"Rossi","year":"2013","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nri3908","article-title":"How leukocytes cross the vascular endothelium","volume":"15","author":"Vestweber","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.ccell.2015.02.015","article-title":"Macrophages and therapeutic resistance in cancer","volume":"27","author":"Ruffell","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.4049\/jimmunol.1201064","article-title":"The prolyl hydroxylase PHD3 identifies proinflammatory macrophages and its expression is regulated by activin A","volume":"189","author":"Escribese","year":"2012","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5092","DOI":"10.1182\/blood-2010-09-306993","article-title":"Activin A skews macrophage polarization by promoting a proinflammatory phenotype and inhibiting the acquisition of anti-inflammatory macrophage markers","volume":"117","author":"Blanco","year":"2011","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/cvr\/cvm102","article-title":"Endothelial sprouting and angiogenesis: Matrix metalloproteinases in the lead","volume":"78","author":"Koolwijk","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1016\/j.bbagen.2014.03.007","article-title":"Matrix metalloproteinases in inflammation","volume":"1840","author":"Nissinen","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"23824","DOI":"10.1016\/S0021-9258(20)80459-1","article-title":"Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages","volume":"268","author":"Shapiro","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.4049\/jimmunol.1201133","article-title":"Serotonin skews human macrophage polarization through HTR2B and HTR7","volume":"190","author":"Bragado","year":"2013","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/path.4466","article-title":"Macrophages from the synovium of active rheumatoid arthritis exhibit an activin A-dependent pro-inflammatory profile","volume":"235","author":"Palacios","year":"2015","journal-title":"J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1006\/bbrc.2001.5161","article-title":"Induction of human matrix metalloproteinase-12 gene transcriptional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells","volume":"285","author":"Wu","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.4049\/jimmunol.1700672","article-title":"Gingival tissue inflammation promotes increased matrix metalloproteinase-12 production by CD200Rlow monocyte-derived cells in periodontitis","volume":"199","author":"Clark","year":"2017","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/joim.12655","article-title":"Integrative studies implicate matrix metalloproteinase-12 as a culprit gene for large-artery atherosclerotic stroke","volume":"282","author":"Mahdessian","year":"2017","journal-title":"J. Intern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"122742","DOI":"10.1172\/jci.insight.122742","article-title":"Cardiovascular protection in females linked to estrogen-dependent inhibition of arterial stiffening and macrophage MMP12","volume":"4","author":"Liu","year":"2019","journal-title":"JCI Insight"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2741\/4378","article-title":"Regulation and involvement of matrix metalloproteinases in vascular diseases","volume":"21","author":"Amin","year":"2016","journal-title":"Front. Biosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e001040","DOI":"10.1161\/JAHA.112.001040","article-title":"Carotid atherosclerotic plaque matrix metalloproteinase-12-positive macrophage subpopulation predicts adverse outcome after endarterectomy","volume":"1","author":"Scholtes","year":"2012","journal-title":"J. Am. Heart Assoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1161\/ATVBAHA.110.219147","article-title":"A selective matrix metalloproteinase-12 inhibitor retards atherosclerotic plaque development in apolipoprotein E-knockout mice","volume":"31","author":"Johnson","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1002\/art.20562","article-title":"Matrix metalloproteinase 12-dependent cleavage of urokinase receptor in systemic sclerosis microvascular endothelial cells results in impaired angiogenesis","volume":"50","author":"Fibbi","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1002\/art.27522","article-title":"Modulation of the angiogenic phenotype of normal and systemic sclerosis endothelial cells by gain-loss of function of pentraxin 3 and matrix metalloproteinase 12","volume":"62","author":"Margheri","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_32","first-page":"3948","article-title":"Protective effects of matrix metalloproteinase-12 following corneal injury","volume":"126","author":"Chan","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.18632\/oncotarget.1987","article-title":"Melanoma cell therapy: Endothelial progenitor cells as shuttle of the MMP12 uPAR-degrading enzyme","volume":"5","author":"Laurenzana","year":"2014","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.exer.2017.04.007","article-title":"Effects of MMP12 on cell motility and inflammation during corneal epithelial repair","volume":"160","author":"Wolf","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19027","DOI":"10.1016\/S0021-9258(18)41732-2","article-title":"Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells","volume":"267","author":"Cheifetz","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/eji.1830220216","article-title":"Regulated expression on human macrophages of endoglin, an Arg-Gly-Asp-containing surface antigen","volume":"22","author":"Lastres","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"ref_37","first-page":"154","article-title":"Endoglin: A 180-kD endothelial cell and macrophage restricted differentiation molecule","volume":"90","author":"McKenzie","year":"1992","journal-title":"Clin. Exp. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1080\/14728222.2017.1365839","article-title":"Endoglin and alk1 as therapeutic targets for hereditary hemorrhagic telangiectasia","volume":"21","author":"Rossi","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"H959","DOI":"10.1152\/ajpheart.01251.2009","article-title":"The physiological role of endoglin in the cardiovascular system","volume":"299","author":"Bernabeu","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/nm1429","article-title":"Soluble endoglin contributes to the pathogenesis of preeclampsia","volume":"12","author":"Venkatesha","year":"2006","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.bbadis.2009.07.003","article-title":"The emerging role of TGF-beta superfamily coreceptors in cancer","volume":"1792","author":"Bernabeu","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/PL00012413","article-title":"Inducible expression of human endoglin during inflammation and wound healing in vivo","volume":"51","author":"Torsney","year":"2002","journal-title":"Inflamm. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12172","DOI":"10.1038\/s41598-017-12491-4","article-title":"A single sphingomyelin species promotes exosomal release of endoglin into the maternal circulation in preeclampsia","volume":"7","author":"Ermini","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.arcmed.2009.07.010","article-title":"Elevated circulating and synovial fluid endoglin are associated with primary knee osteoarthritis severity","volume":"40","author":"Honsawek","year":"2009","journal-title":"Arch. Med. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bl\u00e1zquez-Medela, A.M., Garc\u00eda-Ortiz, L., G\u00f3mez-Marcos, M.A., Recio-Rodr\u00edguez, J.I., S\u00e1nchez-Rodr\u00edguez, A., L\u00f3pez-Novoa, J.M., and Mart\u00ednez-Salgado, C. (2010). Increased plasma soluble endoglin levels as an indicator of cardiovascular alterations in hypertensive and diabetic patients. BMC Med., 8.","DOI":"10.1186\/1741-7015-8-86"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1016\/j.placenta.2013.10.020","article-title":"Review: The enigmatic role of endoglin in the placenta","volume":"35","author":"Gregory","year":"2014","journal-title":"Placenta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"dmm034397","DOI":"10.1242\/dmm.034397","article-title":"Soluble endoglin regulates expression of angiogenesis-related proteins and induction of arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia","volume":"11","author":"Botella","year":"2018","journal-title":"Dis. Models Mech."},{"key":"ref_48","first-page":"1189","article-title":"TNF alpha down-regulates CD105 expression in vascular endothelial cells: A comparative study with TGF beta 1","volume":"23","author":"Li","year":"2003","journal-title":"Anticancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.cyto.2011.06.003","article-title":"Tumor necrosis factor \u03b1 induces a model of preeclampsia in pregnant baboons (Papio hamadryas)","volume":"56","author":"Sunderland","year":"2011","journal-title":"Cytokine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3970","DOI":"10.1038\/onc.2013.386","article-title":"Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-\u03b2 signaling","volume":"33","author":"Kumar","year":"2014","journal-title":"Oncogene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s10456-016-9495-8","article-title":"Transcription factor KLF6 upregulates expression of metalloprotease MMP14 and subsequent release of soluble endoglin during vascular injury","volume":"19","author":"Blanco","year":"2016","journal-title":"Angiogenesis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.lfs.2017.03.014","article-title":"Soluble endoglin modulates the pro-inflammatory mediators NF-\u03baB and IL-6 in cultured human endothelial cells","volume":"175","author":"Varejckova","year":"2017","journal-title":"Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1158\/0008-5472.CAN-09-4466","article-title":"Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis","volume":"70","author":"Hawinkels","year":"2010","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1159\/000448996","article-title":"High levels of soluble endoglin induce a proinflammatory and oxidative-stress phenotype associated with preserved NO-dependent vasodilatation in aortas from mice fed a high-fat diet","volume":"53","author":"Jezkova","year":"2016","journal-title":"J. Vasc. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.atherosclerosis.2018.02.008","article-title":"Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall dysfunction in mouse aorta","volume":"271","author":"Vitverova","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1021\/jm900093d","article-title":"A selective matrix metalloprotease 12 inhibitor for potential treatment of chronic obstructive pulmonary disease (COPD): Discovery of (S)-2-(8-(methoxycarbonylamino)dibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoic acid (MMP408)","volume":"52","author":"Li","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1161\/CIRCULATIONAHA.112.101261","article-title":"Oxysterol-induced soluble endoglin release and its involvement in hypertension","volume":"126","author":"Blanco","year":"2012","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrcardio.2017.52","article-title":"Monocytes and macrophages in abdominal aortic aneurysm","volume":"14","author":"Raffort","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s11883-016-0585-2","article-title":"Macrophages in vascular inflammation: Origins and functions","volume":"18","author":"Decano","year":"2016","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1002\/art.20567","article-title":"Association of increased expression of macrophage elastase (matrix metalloproteinase 12) with rheumatoid arthritis","volume":"50","author":"Liu","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"59","DOI":"10.14712\/18059694.2016.19","article-title":"Serum level of a soluble form of endoglin (CD105) is decreased after Goeckerman\u2019s therapy of psoriasis","volume":"54","author":"Pohl","year":"2011","journal-title":"Acta Med. (Hradec Kral.)"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0923-1811(95)00397-B","article-title":"Expression of endoglin in psoriatic involved and uninvolved skin","volume":"10","author":"Rulo","year":"1995","journal-title":"J. Dermatol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/00015559850135760","article-title":"Expression of endoglin in the transition between psoriatic uninvolved and involved skin","volume":"78","author":"Rulo","year":"1998","journal-title":"Acta Derm. Venereol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ojeda-Fern\u00e1ndez, L., Recio-Poveda, L., Aristorena, M., Lastres, P., Blanco, F.J., Sanz-Rodr\u00edguez, F., Gallardo-Vara, E., de las Casas-Engel, M., Corb\u00ed, \u00c1., and Arthur, H.M. (2016). Mice lacking endoglin in macrophages show an impaired immune response. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1005935"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1086\/511645","article-title":"Hemorrhagic hereditary telangiectasia (Rendu-Osler disease) and infectious diseases: An underestimated association","volume":"44","author":"Giraud","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.blre.2010.07.001","article-title":"Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment","volume":"24","author":"Shovlin","year":"2010","journal-title":"Blood Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"767185","DOI":"10.1155\/2014\/767185","article-title":"Impaired resolution of inflammation in the Endoglin heterozygous mouse model of chronic colitis","volume":"2014","author":"Peter","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3389\/fgene.2014.00457","article-title":"Endoglin involvement in integrin-mediated cell adhesion as a putative pathogenic mechanism in hereditary hemorrhagic telangiectasia type 1 (HHT1)","volume":"5","author":"Rossi","year":"2015","journal-title":"Front. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1161\/CIRCULATIONAHA.106.639161","article-title":"Endoglin has a crucial role in blood cell-mediated vascular repair","volume":"114","author":"Post","year":"2006","journal-title":"Circulation"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.gene.2019.02.016","article-title":"Characterization of a mutation in the zona pellucida module of endoglin that causes hereditary hemorrhagic telangiectasia","volume":"696","author":"Chiapparino","year":"2019","journal-title":"Gene"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"29197","DOI":"10.1074\/jbc.M111991200","article-title":"Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II","volume":"277","author":"Letamendia","year":"2002","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/12\/3107\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:01:09Z","timestamp":1760187669000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/12\/3107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,25]]},"references-count":72,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["ijms20123107"],"URL":"https:\/\/doi.org\/10.3390\/ijms20123107","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,25]]}}}