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Figure 1. Vein wall, venous valves and blood flow in normal veins and VVs. In normal veins, competent venous valves allow blood flow in an antegrade direction towards the heart (A). In CVD, vein dysfunction could progress to large dilated VVs with incompetent valves. VVs show atrophic regions where increases in MMP levels promote ECM degradation, as well as hypertrophic regions in which MMP/TIMP imbalance would allow ECM accumulation, leading to dilated and tortuous vein wall, defective valves, and venous reflux (B). VVs: Varicose veins; CVD: chronic venous disease; MMP: matrix metalloproteinases; ECM: extracellular matrix; TIMP: tissue inhibitors of metalloproteinase.