Daniel and colleagues asked whether FSAP may influence factors involved in pericellular proteolysis. They studied the influence of FSAP on the expression of uPA, tPA, MMP-2 and -9 (gelatinases) in cultured endothelial cells (EC) and vascular smooth muscle cells (VSMC). Studies were also performed in the mouse vascular injury model.

FSAP was found to activate pro-uPA to uPA but, over time, to decrease the activity of uPA in cultured EC and VSMC. Protein levels of uPA were reduced and the enzymatic activity of FSAP was required for this. In contrast, an increase in the gelatinase activity (MMP-2 and -9) was observed, without changes in the levels of individual proteins. FSAP caused this through a non-proteolytic mechanism. However, there was no regulation of the mRNA levels for uPA, tPA, MMP-2 and -9. Also the levels of the gelatinase inhibitors, i.e. the tissue inhibitors of matrix metalloproteinases (TIMPs), were not affected. In a similar manner as in vitro, FSAP reduced uPA activity and increased gelatinase activity in vessel walls in the mouse vascular injury model.

Title:
Factor Seven activating protease (FSAP); A key regulator of pericellular proteolysis.

Authors and Source:
J Daniel, O Uslu, K Hersemeyer, O Rannou, L Muhl, KT Preissner, D Sedding, SM Kanse
Poster presentation ISTH 2009: AS-TH-058