{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:44:33Z","timestamp":1785300273735,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T00:00:00Z","timestamp":1458000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Wound Journal"],"published-print":{"date-parts":[[2017,2]]},"abstract":"Abstract<\/jats:title>Chronic venous disease (CVD<\/jats:styled-content>) and its most frightening complication, chronic venous ulceration (CVU<\/jats:styled-content>), represent an important socioeconomic burden in the western world. Metalloproteinases have been identified in the pathogenesis of several vascular diseases such as venous problems. The aim of this study was to evaluate a broad range of metalloproteinases, such as matrix metalloproteinases (MMPs<\/jats:styled-content>), ADAMs<\/jats:styled-content> (a disintegrin and metalloproteinases) and ADAMTSs<\/jats:styled-content> (a disintegrin and metalloproteinases with thrombospondin motifs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs<\/jats:styled-content>) and a related protein, neutrophil gelatinase\u2010associated lipocalin (NGAL<\/jats:styled-content>), in patients with CVD<\/jats:styled-content> in order to correlate their serum levels with each stage of the disease. We performed a multicenter open\u2010label study that comprised the enrolment of 541 patients with CVD<\/jats:styled-content> of clinical stages C1\u2013C6<\/jats:styled-content>, (178 males, 363 females; mean age 57\u00b729, median age 53\u00b772, age range 29\u201381); 29 subjects without CVD<\/jats:styled-content> were included in this study (9 males and 20 females; mean age 54\u00b744, median age 50, age range 28\u201384) as the control group. Enzyme\u2010linked immunosorbent assay (ELISA<\/jats:styled-content>) was performed for measuring serum levels of proteases and related proteins. The study found that the serum elevation of MMP<\/jats:styled-content>\u20102, ADAMTS<\/jats:styled-content>\u20101 and ADAMTS<\/jats:styled-content>\u20107 appeared to be correlated with the initial stages of CVD<\/jats:styled-content>, whereas the serum elevation of MMP<\/jats:styled-content>\u20101, MMP<\/jats:styled-content>\u20108, MMP<\/jats:styled-content>\u20109, NGAL<\/jats:styled-content>, ADAM<\/jats:styled-content>\u201010, ADAM<\/jats:styled-content>\u201017 and ADAMTS<\/jats:styled-content>\u20104 was particularly involved in skin change complications. This study showed that each stage of CVD<\/jats:styled-content> may be described by particular patterns of metalloproteinases, and this may have therapeutic implications in discovering new targets and new drugs for the treatment of CVD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/iwj.12594","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T00:56:41Z","timestamp":1458349001000},"page":"233-240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["From varices to venous ulceration: the story of chronic venous disease described by metalloproteinases"],"prefix":"10.1111","volume":"14","author":[{"given":"Raffaele","family":"Serra","sequence":"first","affiliation":[{"name":"Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology University Magna Graecia of Catanzaro Catanzaro Italy"},{"name":"Department of Medical and Surgical Sciences University of Catanzaro Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Gallelli","sequence":"additional","affiliation":[{"name":"Department of Health Sciences University of Catanzaro Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Butrico","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Catanzaro Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6998-5405","authenticated-orcid":false,"given":"Gianluca","family":"Buffone","sequence":"additional","affiliation":[{"name":"Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology University Magna Graecia of Catanzaro Catanzaro Italy"},{"name":"Department of Medical and Surgical Sciences University of Catanzaro Catanzaro Italy"},{"name":"Department of Health Sciences University of Catanzaro Catanzaro Italy"},{"name":"Division of Vascular Surgery Sant'Anna Hospital Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco G","family":"Cali\u00f2","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery Sant'Anna Hospital Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"De Caridi","sequence":"additional","affiliation":[{"name":"Cardiovascular and Thoracic Department, Policlinico G. Martino Hospital University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafalda","family":"Massara","sequence":"additional","affiliation":[{"name":"Cardiovascular and Thoracic Department, Policlinico G. Martino Hospital University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Barbetta","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Catanzaro Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Amato","sequence":"additional","affiliation":[{"name":"Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology University Magna Graecia of Catanzaro Catanzaro Italy"},{"name":"Department of Clinical Medicine and Surgery University Federico II of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Labonia","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Catanzaro Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena","family":"Mimmi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Catanzaro Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Iaccino","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Catanzaro Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"de Franciscis","sequence":"additional","affiliation":[{"name":"Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology University Magna Graecia of Catanzaro Catanzaro Italy"},{"name":"Department of Medical and Surgical Sciences University of Catanzaro Catanzaro 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