title: Mechanisms of varicose vein formation: valve dysfunction and wall dilation.
abstract: Varicose veins are a common venous disease of the lower extremity. Although the mechanisms and determinants in the development of varicosities are not clearly defined, recent clinical studies and basic science research have cast some light on possible mechanisms of the disease. In varicose veins, there are reflux and incompetent valves as well as vein wall dilation. Primary structural changes in the valves may make them 'leaky', with progressive reflux causing secondary changes in the vein wall. Alternatively, or concurrently, the valves may become incompetent secondary to structural abnormalities and focal dilation in vein wall segments near the valve junctions, and the reflux ensues as an epiphenomenon. The increase in venous pressure causes structural and functional changes in the vein wall that leads to further venous dilation. Increase in vein wall tension augments the expression/activity of matrix metalloproteinases (MMPs), which induces degradation of the extracellular matrix proteins and affect the structural integrity of the vein wall. Recent evidence also suggests an effect of MMPs on the endothelium and smooth muscle components of the vein wall and thereby causing changes in the venous constriction/relaxation properties. Endothelial cell injury also triggers leukocyte infiltration, activation and inflammation, which lead to further vein wall damage. Thus, vein wall dilation appears to precede valve dysfunction, and the MMP activation and superimposed inflammation and fibrosis would then lead to chronic and progressive venous insufficiency and varicose vein formation.
authors.affiliation: Division of Vascular Surgery, VA Boston Healthcare System, Surgery 112, 1400 VFW Parkway, West Roxbury, MA 02132, USA. joseph.raffetto@med.va.gov
authors.forename: J D
authors.initials: JD
authors.lastname: Raffetto
authors.forename: R A
authors.initials: RA
authors.lastname: Khalil
mesh_terms: D000818:Animals; D017209:Apoptosis; D004108:Dilatation, Pathologic; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D014648:Varicose Veins / Q000503:physiopathology*; D014689:Venous Insufficiency / Q000503:physiopathology*; D014690:Venous Pressure
chemical_list: D020782:Matrix Metalloproteinases