{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:21:20Z","timestamp":1791321680914,"version":"4.3.1"},"reference-count":114,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2009,10,21]],"date-time":"2009-10-21T00:00:00Z","timestamp":1256083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000297","name":"Royal College of Surgeons of England","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000297","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees' Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Valvular incompetence and reflux are common features of primary varicose veins, and have long been thought to be their cause. Recent evidence, however, suggests that changes in the vein wall may precede valvular dysfunction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A literature search was performed using PubMed and Ovid using the keywords \u2018varicose vein wall changes\u2019, \u2018pathogenesis\u2019, \u2018aetiology\u2019 and \u2018valvular dysfunction\u2019. Articles discussing the pathophysiology of complications of varicose veins, such as ulceration, recurrence, thrombophlebitis and lipodermatosclerosis, were excluded.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results and conclusion<\/jats:title>\n                  <jats:p>Positive family history, age, sex and pregnancy are important risk factors for varicose vein formation. Areas of intimal hyperplasia and smooth muscle cell proliferation are often noted in varicose veins, although regions of atrophy are also present. The total elastin content in varicose as opposed to non-varicose veins is reduced; changes in overall collagen content are uncertain. Matrix metalloproteinases (MMPs), including MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9, and tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-3 are upregulated in varicose veins. Activation of the endothelium stimulates the recruitment of leucocytes and the release of growth factors, leading to smooth muscle cell proliferation and migration. Dysregulated apoptosis has also been demonstrated in varicose veins. An understanding of the pathophysiology of varicose veins is important in the identification of potential therapeutic targets and treatment strategies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/bjs.6798","type":"journal-article","created":{"date-parts":[[2009,10,21]],"date-time":"2009-10-21T13:46:53Z","timestamp":1256132813000},"page":"1231-1242","source":"Crossref","is-referenced-by-count":234,"title":["Pathogenesis of primary varicose veins"],"prefix":"10.1093","volume":"96","author":[{"given":"C S","family":"Lim","sequence":"first","affiliation":[{"name":"Imperial Vascular Unit, Imperial College London, 4 East, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A H","family":"Davies","sequence":"additional","affiliation":[{"name":"Imperial Vascular Unit, Imperial College London, 4 East, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,10,21]]},"reference":[{"key":"2021070906280555300_bib1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1136\/jech.53.3.149","article-title":"Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study","volume":"53","author":"Evans","year":"1999","journal-title":"J Epidemiol Community Health"},{"key":"2021070906280555300_bib2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0895-4356(02)00518-8","article-title":"Lifestyle factors and the risk of varicose veins: Edinburgh Vein Study","volume":"564","author":"Lee","year":"2003","journal-title":"J Clin Epidemiol"},{"key":"2021070906280555300_bib3","first-page":"23","article-title":"The management of chronic venous disorders of the leg: an evidence-based report of an international task force. 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