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Angioedema attacks result from increased vascular permeability due to the release of bradykinin from high molecular weight kininogen. Currently, there are no biomarkers predicting the frequency of angioedema attacks. Vascular permeability is modulated by several factors, including vascular endothelial growth factors (VEGF<\/jats:styled-content>s) and angiopoietins (Angs). As increased circulating levels of VEGF<\/jats:styled-content>s and Angs have been observed in diseases associated with higher vascular permeability (e.g., systemic capillary leak syndrome and sepsis), we sought to analyze plasma concentrations of VEGF<\/jats:styled-content>s and Angs in patients with C1\u2010INH<\/jats:styled-content>\u2010HAE<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Sixty\u2010eight healthy controls and 128 patients with C1\u2010INH<\/jats:styled-content>\u2010HAE<\/jats:styled-content> were studied. Concentrations of angiogenic (VEGF<\/jats:styled-content>\u2010A, Ang1, Ang2), anti\u2010angiogenic (VEGF<\/jats:styled-content>\u2010A165b<\/jats:sub>) and lymphangiogenic (VEGF<\/jats:styled-content>\u2010C) factors were evaluated by ELISA<\/jats:styled-content>. C1\u2010INH<\/jats:styled-content> functional activity was assessed by EIA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>Plasma concentrations of VEGF<\/jats:styled-content>\u2010A, VEGF<\/jats:styled-content>\u2010C, Ang1, and Ang2 were higher in patients with C1\u2010INH<\/jats:styled-content>\u2010HAE<\/jats:styled-content> in remission than in healthy controls. Concentration of VEGF<\/jats:styled-content>\u2010A was further increased in patients with lower C1\u2010INH<\/jats:styled-content> functional activity. Patients with C1\u2010INH<\/jats:styled-content>\u2010HAE<\/jats:styled-content> experiencing more than 12 angioedema attacks per year were characterized by higher plasma levels of VEGF<\/jats:styled-content>\u2010A, VEGF<\/jats:styled-content>\u2010C, and Ang2 compared with the other patients.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>We hypothesize that VEGF<\/jats:styled-content>s and Angs induce a state of \u2018vascular preconditioning\u2019 that may predispose to angioedema attacks. In addition, the identification of increased plasma levels of VEGF<\/jats:styled-content>s and Angs in patients with C1\u2010INH<\/jats:styled-content>\u2010HAE<\/jats:styled-content> may prompt the investigation of VEGF<\/jats:styled-content>s and Angs as biomarkers of C1\u2010INH<\/jats:styled-content>\u2010HAE<\/jats:styled-content> severity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.12862","type":"journal-article","created":{"date-parts":[[2016,2,13]],"date-time":"2016-02-13T14:52:43Z","timestamp":1455375163000},"page":"989-996","source":"Crossref","is-referenced-by-count":53,"title":["Elevated plasma levels of vascular permeability factors in C1 inhibitor\u2010deficient hereditary angioedema"],"prefix":"10.1111","volume":"71","author":[{"given":"S.","family":"Loffredo","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI) University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bova","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI) University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Suffritti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Luigi Sacco Luigi Sacco Hospital Milan University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Borriello","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI) University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Zanichelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Luigi Sacco Luigi Sacco Hospital Milan University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Petraroli","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI) University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Varricchi","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI) University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Triggiani","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology University of Salerno Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Cicardi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Luigi Sacco Luigi Sacco Hospital Milan University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Marone","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI) University of Naples Federico II Naples Italy"},{"name":"CNR Institute of Experimental Endocrinology and Oncology \u2018G. 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