Figure 1.

Factors leading to hypertension in response to placental ischemia. Placental ischemia is associated with increases in several factors, such as matrix metalloproteinases (MMPs), angiotensin II type 1 receptor autoantibody (AT1-AA), tumor necrosis factor-α (TNF-α), soluble endoglin, and soluble fms-like tyrosine kinase-1 (sFlt-1). MMPs cleave big endothelin to active endothelin. These circulating factors lead to increased levels of vascular endothelin-1 (ET-1) expression and subsequent ET_A activation, resulting in hypertension. ET antagonists may reduce hypertension, therefore improving maternal and fetal outcomes.