Role of proteases in dysfunctional placental vascular remodelling in preeclampsia

Abstract

Preeclampsia is a syndrome characterised by vascular dysfunction, impaired angiogenesis, and hypertension during pregnancy. Even when the precise pathophysiology of preeclampsia remains elusive, impaired vascular remodelling and placental angiogenesis in the placental villi and defective trophoblast invasion of the uterus are proposed as crucial mechanisms in this syndrome. Reduced trophoblast invasion leads to reduced uteroplacental blood flow and oxygen availability and increased oxidative stress. These phenomena trigger the release of soluble factors into the maternal and foetoplacental circulation that are responsible of the clinical features of preeclampsia. New blood vessels generation as well as vascular remodelling are mechanisms that require expression and activity of different proteases, including matrix metalloproteases, a-disintegrin and metalloproteases, and a-disintegrin and metalloprotease with thrombospondin motifs. These proteases exert proteolysis of the extracellular matrix. Additionally, cathepsins, a family of proteolytic enzymes, are primarily located in lysosomes but are also released by cells to the extracellular space. This review focuses on the role that these proteases play in the regulation of the uterine trophoblast invasion and the placental vascular remodelling associated with preeclampsia.