The Role of Matrix Metalloproteinase-2 in the Pathophysiology of a Reduced Utero-Placental Perfusion Pressure Model of Preeclampsia
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Abstract
Preeclampsia is a leading cause of maternal and fetal morbidity/mortality and induced preterm birth. Endothelin-1 (ET-1) is a potent vasoactive agent, shown to be involved in the vascular endothelial dysfunction of preeclampsia. Big endothelin (bigET) is cleaved to ET-1 by several enzymes including matrix metalloproteinase-2 (MMP-2). I hypothesized that increased levels and/or activity of MMP-2 may lead to enhanced production of ET-1 and thus increase vasoconstriction in preeclampsia. I used the reduced utero-placental perfusion pressure (RUPP) model of preeclampsia and studied vascular function using mesenteric arteries from Sham and RUPP to test my hypothesis. I showed that: 1) vascular contractility in response to bigET was greater in RUPP, 2) the contribution of MMP-2 to bigET to ET-1 cleavage was greater in RUPP, 3) nitric oxide can modulate the function of MMP-2 and several other bigET cleaving enzymes. These novel findings can provide avenues for new therapeutic approaches to preeclampsia.