{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:21:18Z","timestamp":1791321678090,"version":"4.3.1"},"reference-count":36,"publisher":"SAGE Publications","issue":"6_suppl","license":[{"start":{"date-parts":[[2005,2,1]],"date-time":"2005-02-01T00:00:00Z","timestamp":1107216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Angiology"],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:p>The mechanisms regulating varicose vein development and the subsequent skin sequelae seen in chronic venous disease (CVD) have been investigated recently. Despite the diversity of signs and symptoms associated with the disease, it seems likely that they are related to venous hypertension. Valvular incompetence is the most important cause of venous hypertension. Recent findings suggest that inflammatory processes are involved in the structural remodeling in venous valves and in the vein wall, leading to valvular incompetence and the development of varicose veins. This has been shown by Ono and colleagues, who found infiltration of valve leaflets and the venous wall by leukocytes (monocytes and tissue macrophages) in all valve specimens from patients with CVD and in none from controls. Further work by Takase and colleagues confirmed this hypothesis. Vein wall remodeling is likely to involve the complex interplay of a range of factors, including an altered ratio between metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), and elevated levels of cytokines and growth factors favor an alteration of the extracellular matrix. Neutrophils and mast cells and their interaction with the venous endothelium are believed to play an important role in the initiation of the inflammatory response in CVD. The transmission of high venous pressures to the dermal microcirculation results in the stimulation of an inflammatory process in which cytokine and growth factor release leads to leukocyte migration into the interstitium and the initiation of further inflammatory events. This process is associated with the intense dermal fibrosis and tissue remodeling seen in chronic venous insufficiency. The many manifestations of the disease are frequently associated with symptoms usually ascribed to CVD. The proportion of patients with symptoms increases with increasing CEAP clinical classes, but the mechanisms underlying symptom appearance have not been elucidated. It has been postulated that it is related to the inflammatory cascade of events seen at all stages of CVD and in which the leukocyte and its interaction with the endothelium play a key role. It is increasingly believed that the emerging twin themes of disturbed venous flow patterns and chronic inflammation underlie and link all the manifestations of the disease. Among the many pathophysiologic mechanisms at work, the leukocyte-endothelium interactions seem to be important in many aspects of the disease and have been identified as a possible target for pharmacologic intervention. Pharmacologic agents that could attenuate various elements of the inflammatory cascade and inhibit the inflammatory process might offer a greater opportunity to prevent future morbidity. It seems reasonable to speculate that such treatment could reduce the risk of CVD progression if applied as soon as the first symptoms appear.<\/jats:p>","DOI":"10.1177\/00033197050560i103","type":"journal-article","created":{"date-parts":[[2007,6,21]],"date-time":"2007-06-21T21:04:37Z","timestamp":1182459877000},"source":"Crossref","is-referenced-by-count":69,"title":["Chronic Venous Disease and the Leukocyte-Endothelium Interaction: From Symptoms to Ulceration"],"prefix":"10.1177","volume":"56","author":[{"given":"A. N.","family":"Nicolaides","sequence":"first","affiliation":[{"name":"The Cyprus Institute of Neurology and Genetics, Cyprus, anicolai@cing.ac.cy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2005,2]]},"reference":[{"key":"e_1_2_1_2_1","unstructured":"Ramelet AA Kern P Perrin M eds: Les varices et t\u00e9langiectasies (in French). 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