“…In class 4 liposclerotic limbs, changes in the structure and also a decreased number of capillaries have been shown, 31 as well as increased leakage from these capillaries into surrounding tissue. 32 In limbs with severe CVD, studies have demonstrated the destruction of the superficial lymphatic plexus, 33 tissue hypoxia, [34][35][36] decreased fibrinolytic activity, [37][38][39] extravasation and pericapillary deposition of fibrin, [40][41][42] accumulation of other substances such as laminin, fibronectin, tenascin, and collagen, 43,44 and activation of leukocytes and endothelial cells, which leads to the degranulation of proteolytic enzymes and release of free radicals that damage the capillary wall. 45,46 Local skin dysfunction could also be attributed to the collagen deposition from fibroblasts that have been activated through leukocytes that release active transforming growth factor-β 1 .…”