Lipodermatosclerosis and the significance of proteolytic remodeling in thepathogenesis of venous ulceration (Review)

The preceding stage of venous ulceration represents a scleroderma-like hard ening of the skin called lipodermatosclerosis. Clinical stages such as lipo dermatosclerosis and venous ulceration, which succeed one another ale highl y associated to chronic venous insufficiency. Lipodermatosclerosis is chara cterized by fibrous scar tissue of the reticular dermis built up of collage n bundles and loss of cellular components, whereas venous ulceration is cha racterized by total loss of epidermis and partially of matrix structures in the upper dermis. There is a growing recognition that an excessive proteol ytic activity by proteases, in particular that of matrix metalloproteinases and fibrinolytic factors of the plasminogen activation system may be a key feature in the pathophysiological understanding of venous leg ulcer format ion. Lipodermatosclerosis displays an intense ongoing proteolytic process b y elevated matrix metalloproteinase activity, as recently shown on differen t molecular and biological levels. Elevated expression on mRNA and protein level of matrix metalloproteinases and fibrinolytic factors of the plasmino gen activation system have been detected in liposclerotic skin lesions. In addition, matrix metalloproteinases were proteolytically activated confirme d by zymography experiments and collagen degradation assays. Therefore it i s well conceivable, that proteolytic enzymes of matrix metalloproteinases c ould initiate an elevated turnover of the extracellular matrix with subsequ ent breakdown of the matrix scaffold finally resulting in venous ulceration .