Lipodermatosclerosis and the significance of proteolytic remodeling in the pathogenesis of venous ulceration (Review).
The preceding stage of venous ulceration represents a scleroderma-like hardening of the skin called lipodermatosclerosis. Clinical stages such as lipodermatosclerosis and venous ulceration, which succeed one another are highly associated to chronic venous insufficiency. Lipodermatosclerosis is characterized by fibrous scar tissue of the reticular dermis built up of collagen bundles and loss of cellular components, whereas venous ulceration is characterized by total loss of epidermis and partially of matrix structures in the upper dermis. There is a growing recognition that an excessive proteolytic 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 formation. Lipodermatosclerosis displays an intense ongoing proteolytic process by elevated matrix metalloproteinase activity, as recently shown on different molecular and biological levels. Elevated expression on mRNA and protein level of matrix metalloproteinases and fibrinolytic factors of the plasminogen activation system have been detected in liposclerotic skin lesions. In addition, matrix metalloproteinases were proteolytically activated confirmed by zymography experiments and collagen degradation assays. Therefore it is well conceivable, that proteolytic enzymes of matrix metalloproteinases could initiate an elevated turnover of the extracellular matrix with subsequent breakdown of the matrix scaffold finally resulting in venous ulceration.
Herouy
Y
Y
Department of Dermatology, University Hospital, 79104-Freiburg, Germany.
Nockowski
P
P
Schöpf
E
E
Norgauer
J
J
D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012594:Scleroderma, Localized / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D014647:Varicose Ulcer / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D010958:Plasminogen; D010450:Endopeptidases; D008666:Metalloendopeptidases