The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis

Abstract

Preeclampsia affects 5%-8% of pregnancies and is the leading worldwide cause of maternal and fetal morbidity and mortality. Preeclampsia is associated with shallow trophoblast invasion and inadequate spiral artery remodeling, which are widely believed to lead to placental hypoxia, the putative culprit initiating the cascade of events that ultimately results in the maternal manifestations of the disease. Despite extensive research, however, the pathophysiology of this disease remains poorly understood, no effective prevention exists, and treatment is limited to symptomatic therapy. Recent research has introduced exciting new theories regarding the pathogenesis of preeclampsia. Clinical and experimental evidence implicating the circulating antiangiogenic molecules soluble Fms-like tyrosine kinase-1 (sFLT-1) and soluble endoglin (sENG), as well as endothelin-1 and the angiotensin II receptor type I autoimmune antibody (AT-1AA), have been especially promising. This review collates evidence for a role of hypoxia and hypoxia-inducible factor-1alpha (HIF1A; referred to as HIF-1α throughout) in the pathogenesis of preeclampsia and discusses possible molecular links between hypoxia and the newly reported potential mediators of the disease's manifestations.