New Insights into the Role of Matrix Metalloproteinases in Preeclampsia

Int J Mol Sci. 2017 Jul 20;18(7):1448. doi: 10.3390/ijms18071448.

Abstract

Preeclampsia is a severe pregnancy complication globally, characterized by poor placentation triggering vascular dysfunction. Matrix metalloproteinases (MMPs) exhibit proteolytic activity implicated in the efficiency of trophoblast invasion to the uterine wall, and a dysregulation of these enzymes has been linked to preeclampsia. A decrease in MMP-2 and MMP-9 interferes with the normal remodeling of spiral arteries at early pregnancy stages, leading to the initial pathophysiological changes observed in preeclampsia. Later in pregnancy, an elevation in MMP-2 and MMP-9 induces abnormal release of vasoactive factors conditioning hypertension. Although these two enzymes lead the scene, other MMPs like MMP-1 and MMP-14 seem to have a role in this pathology. This review gathers published recent evidence about the implications of different MMPs in preeclampsia, and the potential use of these enzymes as emergent biomarkers and biological therapeutic targets, focusing on studies involving human subjects.

Keywords: biomarkers; endothelial damage; implantation; matrix metalloproteinases; preeclampsia; therapeutic targets; trophoblast.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Biomarkers
  • Endothelial Cells / metabolism
  • Female
  • Humans
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Matrix Metalloproteinase Inhibitors / therapeutic use
  • Matrix Metalloproteinases / metabolism*
  • Placenta / metabolism
  • Placentation
  • Pre-Eclampsia / drug therapy
  • Pre-Eclampsia / etiology
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • Trophoblasts / drug effects
  • Trophoblasts / metabolism

Substances

  • Biomarkers
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases