Epigenetics and Preeclampsia: Programming of Future Outcomes.

ABSTRACT

Pregnancy is known to induce rapid, progressive, and substantial changes to the cardiovascular system, ultimately facilitating successful pregnancy outcomes. Women who develop hypertensive disorders during pregnancy are considered to have "failed" the cardiovascular stress test of pregnancy and likely represent a subpopulation with inadequate cardiovascular accommodation. Preeclampsia is a serious complication with a myriad of manifestations in both mother and offspring. This pregnancy syndrome is a polygenic disease and has now been linked to a greater incidence of cardiovascular disease. Moreover, offsprings born to preeclamptic mothers exhibit an elevated risk of cardiovascular disease, stroke, and mental disorders during adulthood. This suggests that preeclampsia not only exposes the mother and the fetus to complications during pregnancy but also programs chronic diseases during adulthood in the offspring. The etiology of preeclampsia remains unknown, with various theories being suggested to explain its origin. It is primarily thought to be associated with poor placentation and entails excessive maternal inflammation and endothelial dysfunction. It is well established now that the maternal immune system and the placenta are involved in a highly choreographed cross talk that underlies adequate spiral artery remodeling required for uteroplacental perfusion and free flow of nutrients to the fetus. Although it is not clear whether immunological alterations occur early during pregnancy, studies have proposed that dysregulated systemic and placental immunity contribute to impaired angiogenesis and the onset of preeclampsia. Recently emerged strong evidence suggests a potential link among epigenetics, microRNAs (miRNAs), and pregnancy complications. This chapter will focus on important aspects of epigenetics, immunological aspects, and cardiovascular and vascular remodeling of preeclampsia.