Matrix metalloproteinases as drug targets in preeclampsia

Abstract

Preeclampsia is an important syndrome complicating pregnancy. While the pathogenesis of preeclampsia is not entirely known, poor placental perfusion leading to widespread maternal endothelial dysfunction is accepted as a major mechanism. It has been suggested that altered placental expression of matrix metalloproteinases (MMPs) may cause shallow cytotrophoblastic invasion and incomplete remodeling of the spiral arteries. MMPs are also thought to link placental ischemia to the cardiovascular alterations of preeclampsia. In fact, MMPs may promote vasoconstriction and surface receptors cleavage affecting the vasculature. Therefore, the overall goal of this review article is to provide an overview of the pathophisiology of preeclampsia, more specifically regarding the role of MMPs in the pathogenesis of preeclampsia and the potential of MMP inhibitors as therapeutic options.

Fig. 1

Possible involvement of MMPs in the pathogenesis of preeclampsia. MMP inhibitors such as doxycycline may prevent the alterations associated with imbalanced MMP activity in preeclampsia. MMP, matrix metalloproteinase; ROS, reactive oxygen species; sFlt-1, soluble fms-like tyrosine kinase-1; VEGFR2, vascular endothelial growth factor receptor-2; β(2)-AR, β(2)-adrenergic receptor; CGRP, calcitonin gene related-peptide; ADM, adrenomedullin; VEGF, vascular endothelial growth factor; PlGF, placental growth factor; NO, nitric oxide.