Hypoxia-Inducible Factor 1 and Preeclampsia: A New Perspective

Purpose of Review Preeclampsia (PE) is a serious and distinct type of pregnancy-induced hypertension, with an incidence of 2-8% worldwide. PE is defined as pregnancy-related hypertension with proteinuria and peripheral edema after 20 weeks of gestation. Hypoxic placenta triggers the release of inflammatory and humoral substances into maternal circulation, leading to induction of oxidative stress, lipid peroxidation, endothelial dysfunction, and peripheral vasoconstriction. The objective of the present narrative review was to find the association between PE and hypoxia-inducible factor 1 (HIF-1) in pregnant women from a new perspective. Recent Findings HIF-1 is the key transcription factor that regulates cellular responses to hypoxia and low oxygen tension. HIF-1 alpha is involved in the differentiation and growth of the placenta mainly in the first and second trimesters. During normal gestation, HIF-1 alpha responds to the alterations in oxygen tension, cytokine, and angiogenic factors release. HIF-1 alpha is considered a key biomarker of placental function and vascularization during pregnancy. Summary HIF-1 alpha plays a crucial role in the pathogenesis of PE through activation of anti-angiogenic and inhibition of proangiogenic factors. As well, HIF-1 alpha increases the expression of the p38MAPK and NLRP3 inflammasomes, which promote placental inflammation and dysfunction. HIF-1 alpha acts as a potential link between inflammatory signaling pathways and the development of PE.