Matrix metalloproteinase-2 is elevated in the plasma of women with preeclampsia

Objective: We have recently demonstrated that matrix metalloproteinase-2 (M MP-2) alters vascular function through cleavage of vasoactive peptides, res ulting in increased vasoconstriction and reduced vasodilation. We, therefor e, hypothesized that MMP levels are increased in women with preeclampsia. I n addition, because vascular endothelial growth factor (VEGF) has been impl icated in the pathophysiology of preeclampsia and is involved in angiogenes is that requires the release of proteases to allow for migration of endothe lial cells, we hypothesized that VEGF increases release of MMPs from endoth elial cells. Methods: We used zymographic analysis to evaluate MMP-2/MMP-9 levels in pla sma of women with preeclampsia (n=12) compared to women with uncomplicated pregnancies (n=12). In addition, we evaluated the changes in the levels of MMP-2 and MMP-9 as well as tissue inhibitors of MMPs (TIMP-1 and TIMP-2) re leased by cultured human umbilical vein endothelial cells in response to VE GF (0.1-10 ng/mL). Results: Our data showed that plasma MMP-2 levels were significantly higher in women with preeclampsia compared to women with uncomplicated pregnancie s (arbitrary intensity units: 690 +/- 111 and 252 +/- 56, respectively, p<0 .05). MMP-9 levels were below the level of detection. In addition, VEGF sti mulated endothelial MMP-2 and MMP-9 release in a concentration- and time-de pendent (6-24 h) manner. Moreover, VEGF stimulation of MMP release occurs w ithout significantly affecting the release of TIMP-1 and TIMP-2. Conclusions: These data suggest that VEGF promotes secretion of MMPs from e ndothelial cells that, in turn, could alter vascular function in women with preeclampsia.