Genetic, immune and vasoactive factors in the vascular dysfunction associated with hypertension in pregnancy

Sajjadh M J Ali, Raouf A Khalil
Expert Opinion on Therapeutic Targets 2015, 19 (11): 1495-515

INTRODUCTION: Preeclampsia (PE) is a major complication of pregnancy that could lead to maternal and fetal morbidity and mortality. The pathophysiological mechanisms of PE are not completely understood, but recent research has begun to unravel some of the potential mechanisms.

AREAS COVERED: Genetic polymorphisms and altered maternal immune response may cause impaired remodeling of the spiral arteries; a potential early defect in PE. Inadequate invasion of cytotrophoblasts into the decidua leads to reduced uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia. Placental ischemia causes the release of biologically active factors such as anti-angiogenic factors, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and angiotensin II receptor autoantibodies. These vasoactive factors could cause systemic vascular endotheliosis and consequent increase in vascular resistance and blood pressure, glomerular endotheliosis causing proteinuria, cerebrovascular endotheliosis causing cerebral edema, seizures and visual disturbances, and hepatic endotheliosis, which may contribute to the manifestations of HELLP syndrome. PE-associated vascular endotheliosis causes a decrease in vasodilator mediators such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor, an increase in vasoconstrictors such as endothelin-1, angiotensin II and thromboxane A2, and enhanced mechanisms of vascular smooth muscle contraction such as intracellular Ca(2+), protein kinase C and Rho-kinase. Changes in matrix metalloproteinase activity and extracellular matrix cause vascular remodeling and further vasoconstriction.

EXPERT OPINION: Some of the genetic, immune and vasoactive factors involved in vascular endotheliosis could be used as biomarkers for early detection, and as potential targets for prevention and treatment of PE.

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