{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T23:15:19Z","timestamp":1774048519756,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T00:00:00Z","timestamp":1513814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001253","name":"European Venous Forum","doi-asserted-by":"publisher","award":["Pump Priming Grant"],"award-info":[{"award-number":["Pump Priming Grant"]}],"id":[{"id":"10.13039\/501100001253","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["SFRH\/SINTD\/60063\/2009"],"award-info":[{"award-number":["SFRH\/SINTD\/60063\/2009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic venous disease (CVeD) is a prevalent condition with a significant socioeconomic burden, yet the pathophysiology is only just beginning to be understood. Previous studies concerning the dysregulation of matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases (TIMPs)) within the varicose vein wall are inconsistent and disregard clinical progression. Moreover, it is highly plausible that MMP and TIMP expression\/activity is affected by transforming growth factor (TGF)-\u03b21 and its signaling receptors (TGF\u03b2Rs) expression\/activity in the vein wall. A case\u2013control study was undertaken to analyze genetic and immunohistochemical differences between healthy (n = 13) and CVeD (early stages: n = 19; advanced stages: n = 12) great saphenous vein samples. Samples were grouped based on anatomic harvest site and subjected to quantitative polymerase chain reaction for MMP1, MMP2, MMP8, MMP9, MMP12, MMP13, TIMP1, TIMP2, TIMP3, TIMP4, TGF\u03b2R1, TGF\u03b2R2, and TGF\u03b2R3 gene expression analysis, and then to immunohistochemistry for immunolocalization of MMP2, TIMP2, and TGF\u03b2R2. Decreased gene expression of MMP12, TIMP2, TIMP3, TIMP4, and TGF\u03b2R2 was found in varicose veins when compared to controls. Regarding CVeD clinical progression, two facts arose: results across anatomical regions were uneven; decreased gene expression of MMP9 and TGF\u03b2R3 and increased gene expression of MMP2 and TIMP3 were found in advanced clinical stages. Most immunohistochemistry results for tunica intima were coherent with qPCR results. In conclusion, decreased expression of TGF\u03b2Rs might suggest a reduction in TGF-\u03b21 participation in the MMP\/TIMP imbalance throughout CVeD progression. Further studies about molecular events in the varicose vein wall are required and should take into consideration the venous anatomical region and CVeD clinical progression.<\/jats:p>","DOI":"10.3390\/ijms19010006","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T12:16:14Z","timestamp":1513858574000},"page":"6","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Variability of MMP\/TIMP and TGF-\u03b21 Receptors throughout the Clinical Progression of Chronic Venous Disease"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8190-5527","authenticated-orcid":false,"given":"Pedro","family":"Serralheiro","sequence":"first","affiliation":[{"name":"Norfolk and Norwich University Hospital, Norwich NR47UY, UK"},{"name":"Faculty of Health Sciences, CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"given":"Ant\u00f3nio","family":"Novais","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4823-5701","authenticated-orcid":false,"given":"Elisa","family":"Cairr\u00e3o","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5658-5445","authenticated-orcid":false,"given":"Cl\u00e1udio","family":"Maia","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"given":"Carlos","family":"Costa Almeida","sequence":"additional","affiliation":[{"name":"Department of General Surgery (C), Coimbra University Hospital Centre, 3041-801 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Ignacio","family":"Verde","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1161\/01.RES.0000070112.80711.3D","article-title":"Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry","volume":"92","author":"Visse","year":"2003","journal-title":"Circ. 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