{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:24:58Z","timestamp":1791015898457,"version":"4.1.0"},"reference-count":211,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"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>One of the early symptoms of chronic venous disease (CVD) is varicose veins (VV) of the lower limbs. There are many etiological environmental factors influencing the development of chronic venous insufficiency (CVI), although genetic factors and family history of the disease play a key role. All these factors induce changes in the hemodynamic in the venous system of the lower limbs leading to blood stasis, hypoxia, inflammation, oxidative stress, proteolytic activity of matrix metalloproteinases (MMPs), changes in microcirculation and, consequently, the remodeling of the venous wall. The aim of this review is to present current knowledge on CVD, including the pathophysiology and mechanisms related to vein wall remodeling. Particular emphasis has been placed on describing the role of inflammation and oxidative stress and the involvement of extracellular hemoglobin as pathogenetic factors of VV. Additionally, active substances used in the treatment of VV were discussed.<\/jats:p>","DOI":"10.3390\/ijms25031560","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T08:56:01Z","timestamp":1706259361000},"page":"1560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3702-1238","authenticated-orcid":false,"given":"Lukasz","family":"Gwozdzinski","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical University of Lodz, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5061-1596","authenticated-orcid":false,"given":"Anna","family":"Pieniazek","sequence":"additional","affiliation":[{"name":"Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2590-7496","authenticated-orcid":false,"given":"Krzysztof","family":"Gwozdzinski","sequence":"additional","affiliation":[{"name":"Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3904\/kjim.2018.230","article-title":"Chronic venous insufficiency and varicose veins of the lower extremities","volume":"34","author":"Youn","year":"2019","journal-title":"Korean J. 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