Pathogenesis of primary varicose veins.
BACKGROUND
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.


METHODS
A literature search was performed using PubMed and Ovid using the keywords 'varicose vein wall changes', 'pathogenesis', 'aetiology' and 'valvular dysfunction'. Articles discussing the pathophysiology of complications of varicose veins, such as ulceration, recurrence, thrombophlebitis and lipodermatosclerosis, were excluded.


CONCLUSIONS
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.
Lim
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CS
Imperial Vascular Unit, Imperial College London, 4 East, Charing Cross Hospital, Fulham Palace Road, London, UK.
Davies
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AH
D017209:Apoptosis; D004730:Endothelium, Vascular / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D006801:Humans; D007866:Leg / Q000098:blood supply*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000209:etiology; D012737:Sex Factors; D014648:Varicose Veins / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D055422:Venous Valves / Q000473:pathology
D020782:Matrix Metalloproteinases