Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction

Abstract

Studies over the last decade have provided exciting new insights into potential mechanisms underlying the pathogenesis of preeclampsia. The initiating event in preeclampsia is generally regarded to be placental ischemia/hypoxia, which in turn results in the elaboration of a variety of factors from the placenta that generates profound effects on the cardiovascular system. This host of molecules includes factors such as soluble fms-like tyrosine kinase-1, the angiotensin II type 1 receptor autoantibody, and cytokines such as tumor necrosis factor-alpha, which generate widespread dysfunction of the maternal vascular endothelium. This dysfunction manifests as enhanced formation of factors such as endothelin, reactive oxygen species, and augmented vascular sensitivity to angiotensin II. Alternatively, the preeclampsia syndrome may also be evidenced as decreased formation of vasodilators such as nitric oxide and prostacyclin. Taken together, these alterations cause hypertension by impairing renal pressure natriuresis and increasing total peripheral resistance. Moreover, the quantitative importance of the various endothelial and humoral factors that mediate vasoconstriction and elevation of arterial pressure during preeclampsia remains to be elucidated. Thus identifying the connection between placental ischemia/hypoxia and maternal cardiovascular abnormalities in hopes of revealing potential therapeutic regimens remains an important area of investigation and will be the focus of this review.

Hypertension in women

“…Subsequent release of placental factors including soluble fms-like tyrosine kinase-1, angiotensin II type 1 receptor autoantibody and cytokines into the maternal circulation leads to widespread dysfunction of the maternal vascular endothelium. 31 Preeclampsia, which is a pregnancy-specific syndrome of exaggerated vasoconstriction and reduced organ perfusion, must be differentiated from pre-existing chronic hypertension as the former can threaten the lives of both mother and fetus, and requires specialized care. 29 Treatment of hypertension during pregnancy, particularly in the second half of gestation, reduces maternal and fetus risk.…”

The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia

“…1,2 The key pathophysiological processes are believed to be initiated by reduced placental perfusion secondary to inadequate trophoblast invasion. 3,4 Placental response to ischemia is manifested by overproduction of anti-angiogenic peptides, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), 5 resulting in a clinical syndrome characterized by widespread systemic endothelial dysfunction.…”

Angiogenic Factors in Superimposed Preeclampsia

“…SPE is associated with even greater maternal and fetal morbidity and mortality than PE in women without preexisting hypertension. 2,5 The pathogenesis of PE, as well as SPE, is likely to involve placental vascular remodeling, leading to defective placentation, 6,7 placental ischemia, 8,9 and maternal endothelial cell dysfunction. 10 Emerging data suggest that placental ischemia is associated with increased production of placental proteins, which, on release into the maternal circulation, cause maternal systemic inflammation and endothelial cell dysfunction.…”