{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T11:17:34Z","timestamp":1793272654576,"version":"4.5.0"},"reference-count":110,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic Venous Disease (CVD) refers to several pathological and hemodynamic alterations of the veins of lower limbs causing a wide range of symptoms and signs with a high prevalence in the general population and with disabling consequences in the most severe forms. The etiology and pathophysiology of CVD is complex and multifactorial, involving genetic, proteomic, and cellular mechanisms that result in changes to the venous structure and functions. Expressions of several genes associated with angiogenesis, vascular development, and the regulation of veins are responsible for the susceptibility to CVD. Current evidence shows that several extracellular matrix alterations (ECM) could be identified and in some cases pharmacologically targeted. This review shows the most up to date information on molecular determinants of CVD in order to provide a complete overview of the current knowledge on this topic. In particular, the article explores the genetic influence, the hormonal influence, ECM imbalance, and histopathology of CVD and the role of endothelial dysfunction in CVD.<\/jats:p>","DOI":"10.3390\/ijms24031928","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T02:51:37Z","timestamp":1674096697000},"page":"1928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Molecular Determinants of Chronic Venous Disease: A Comprehensive Review"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9199-8755","authenticated-orcid":false,"given":"Davide","family":"Costa","sequence":"first","affiliation":[{"name":"Department of Law, Economics and Sociology, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7974-3792","authenticated-orcid":false,"given":"Michele","family":"Andreucci","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1011-9844","authenticated-orcid":false,"given":"Nicola","family":"Ielapi","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Disease, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4804-9570","authenticated-orcid":false,"given":"Giuseppe Filiberto","family":"Serraino","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Mastroroberto","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-9791","authenticated-orcid":false,"given":"Umberto Marcello","family":"Bracale","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4477-7412","authenticated-orcid":false,"given":"Raffaele","family":"Serra","sequence":"additional","affiliation":[{"name":"Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref_1","first-page":"34","article-title":"Epidemiology, diagnosis and treatment of chronic venous disease: A systematic review","volume":"29","author":"Serra","year":"2016","journal-title":"Chirurgia"},{"key":"ref_2","first-page":"9","article-title":"Epidemiology, diagnosis and treatment of chronic leg ulcers: A systematic review","volume":"16","author":"Serra","year":"2015","journal-title":"Acta Phlebolol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jvsv.2019.12.075","article-title":"The 2020 update of the CEAP classification system and reporting standards","volume":"8","author":"Lurie","year":"2020","journal-title":"J. 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