Gene expression of fibrinolytic factors of the urokinase-plasmin-system inlipodermatosclerosis

Dermatoliposclerosis develops as a result of progressive primary varicosis or a postthrombotic syndrome (PTS). in spite of existing indications of mod ified intravascular fibrinolytic activity in chronic venous insufficiency ( CVI), no fibrinolytic factors in the perivascular tissues have been investi gated to date. We recently showed that matrix metalloproteinases are expres sed and activated in dermatoliopsclerosis. Since specific fibrinolytic fact ors are important primary effecters of matrix metalloproteinase activation, we recently investigated the genetic expression of the urokinase-type (uPA ) and tissue-type (tPA) plasminogen activators as well as the urokinase-typ e plasminogen receptor (uPA-R) and plasminogen activator inhibitors (PAI-1 and PAI-2) in tissue biopsies from patients with dermatoliposclerosis. For demonstration we used the technique of reverse transcription and polymerase chain reaction (RT-PCR). All the major samples (n = 21) showed significant ly increased mRNA expression of uPA and uPA-R compared with healthy skin (n = 12). Conversely, no significant difference was shown for mRNA transcript ions of tPA, PAI-1 or PAI-2. Thus dermatoliposclerosis is marked by increas ed transcriptional expression of uPA and uPA-R. Hence, increased de novo sy nthesis of uPA and uPA-R may play a central role in the activation of matri x metalloproteinases, and thus in the pathogenesis of crural ulcers.