Placental ischemia and cardiovascular dysfunction in preeclampsia and beyond: making the connections

Abstract

Hypertensive disorders of pregnancy continue to be a significant source of maternal and fetal morbidity and mortality, and recent evidence suggests that the incidence of preeclampsia (PE) is increasing. Recent epidemiological studies indicate that the effects of PE may persist long after pregnancy, in both the mother and the offspring, as increased incidence of cardiovascular disease. The last decade has produced new insights into the pathogenesis of PE. The initiating event in PE appears to be impaired placental perfusion and subsequent placental ischemia, which results in the elaboration of numerous factors. Factors such as soluble fms-like tyrosine kinase-1, soluble endoglin and the angiotensin II type-1 receptor autoantibodies contribute to maternal endothelial and cardiovascular dysfunction, marked by increased reactive oxygen species and decreased bioavailable VEGF, nitric oxide and prostacyclin. However, the importance of the various endothelial and humoral factors that mediate these changes during PE remain to be elucidated. Keywords cardiac; cytokines; pregnancy; VEGF Clinical significance of the hypertensive disorders of pregnancyPreeclampsia (PE) is a pregnancy-specific syndrome characterized by new-onset hypertension and proteinuria manifesting after 20 weeks of gestation, which may progress and cause injury to the blood vessels of major organs, such as the liver and the brain. The hepatic and neuro logical complications of PE make it a potentially deadly disease, especially when tertiary obstetrical care is lacking. Consequently, PE remains a considerable obstetric problem and a significant source of maternal and neonatal morbidity and mortality [1].

Decreased Cyr61 under hypoxia induces extravillous trophoblasts apoptosis and preeclampsia

“…Hypoxia plays an important role in trophoblast invasion and differentiation. Placental hypoxia triggered by impaired trophoblast invasion is suggested to be involved in the pathophysiology of preeclampsia [1,2] , but the exact mechanism by which trophoblasts sense oxygen tension remains elusive. We attempt to explore how artificial hypoxic stimuli mimic the pathological conditions is attributed to hypoxic stress in vitro.…”

Regulation of the Matricellular Proteins CYR61 (CCN1) and NOV (CCN3) by Hypoxia-Inducible Factor-1α and Transforming-Growth Factor-β3 in the Human Trophoblast

“…Therefore, trophoblast invasion early in pregnancy determines placental oxygenation, and the hypoxic environment determines optimal trophoblast invasion (10). Insufficient trophoblast invasion results in chronic placental hypoxia later in pregnancy, leading to PE (10,11), but the exact mechanism by which trophoblasts sense oxygen tension remains still elusive. The hypoxia-inducible factor-1␣ (HIF-1␣) is highly up-regulated in PE (12) and thereby may regulate invasion-related genes (13).…”

Does transthyretin function as one of contributors for preeclampsia?

“…As written, we consider that some variant TTR proteins may contribute to the deposition of amyloid fibrils in the vascular system, serum TTR monomers aggregate to form amyloidosis, which is assumed to lead to a decrease levels of TTR compared to the women with healthy pregnancy. Besides, liver and placenta ischemia may cause a decrease secretion of TTR [24,25]. Despite the development of obstetrics and neonatal care, there is a need for biomarkers of high predictive value for early diagnosis of the disease.…”