ESM-1 and GBP-1 are associated with endothelial dysfunction: emerging biomarkers or key players in the pathophysiology of preeclampsia?

Abstract

Preeclampsia is a hypertensive disorder of pregnancy and is one of the most prevalent causes of maternal and fetal morbidity and mortality. The disease is thought to originate from impaired placental development or restricted villous perfusion, villous constraints and placental senescence at the end of pregnancy, which in turn cause defective placental functioning and eventually systemic endothelial dysfunction. Because the precise pathophysiology of this pregnancy complication is still not clear and diagnosis is only made when it is clinically visible, considerable research is being performed on biomolecules that could play a role in the development of the disease and could have a predictive, diagnostic or prognostic value. In the present review, we focus on two proteins, associated with endothelial dysfunction, which have changed levels in pregnant women during preeclampsia. These two proteins, endothelial specific molecule-1 (ESM-1) and guanylate binding protein-1 (GBP-1), are known to be involved in processes such as angiogenesis, inflammation and endothelial activation. ESM-1 is increased during preeclampsia and GBP-1 is decreased during preeclampsia, and their potential as biomarkers for preeclampsia could therefore be assessed. In addition to assessing their potential to serve as biomarkers, we will go into potential pathophysiological mechanisms of preeclampsia in which these proteins might be involved. We are proposing that ESM-1 and GBP-1 might play a role in impaired angiogenesis and vascular maladaptation, impaired immune regulation and oxidative stress, which ultimately could lead to endothelial dysfunction and preeclampsia.

Keywords: ESM‐1; GBP‐1; biomarkers; endothelial dysfunction; preeclampsia; pregnancy.