Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies

Abstract

Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2–5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu.

Elevated Blood Pressure in Preterm-Born Offspring Associates With a Distinct Antiangiogenic State and Microvascular Abnormalities in Adult Life

“…19 D'Souza et al 17,[37][38][39] found that infants born later in gestation after maternal preeclampsia, a condition characterized by elevated placental-derived antiangiogenic factors in both maternal and fetal circulations, had capillary rarefaction evident at birth. 40 These observations raise the possibility that the circulating angiogenic state is both altered and directly relevant to vasculogensis in the offspring both pre-and postnatally.…”

Trends in the use of preconditioning to hypoxia for early prevention of future life diseases

“…Many of these works are the epidemiologic studies with great numbers of participants, so the results of the studies are reliable. It was found that abnormalities during pregnancy might give many pathologic consequences for future offspring's life, for example: cardiovascular and cardiopulmonary diseases, including high blood pressure and risk of stroke (1)(2)(3)(4)(5)(23)(24)(25); behavioral, neurological and mental diseases, including cerebral palsy, depression, schizophrenia, epilepsy (24,(26)(27)(28)(29)(30); metabolic diseases, including overweight, type 2 diabetes (2-5,31-33); bronchopulmonary diseases, including asthma (34,35); hearing loss (36). This data show that abnormalities during pregnancy, including obstetric complications and abnormalities of early growth, are associated with or caused by some types of hypoxia.…”

A Maternally Sequestered, Biopolymer‐Stabilized Vascular Endothelial Growth Factor (VEGF) Chimera for Treatment of Preeclampsia

“…This susceptibility to cardiorenal and metabolic diseases post–index pregnancy has been attributed to the pathophysiological mechanisms10, 11 initiated by the placental ischemia. In addition to the maternal effects, preeclampsia is highly associated with intrauterine growth restriction12 and developmentally programs the increased risk for cardiovascular disease,13, 14 stroke,15 renal disease,16 and metabolic dysfunction17, 18 in the adult offspring of preeclamptic women 19. Since the resolution of preeclampsia is achieved only through parturition of the ischemic placenta,20 a difficult decision often must be made between inducing early delivery in order to halt the progression of the syndrome in the mother and risking premature birth complications to the fetus 21.…”