Excessive hypercholesterolaemia during pregnancy as a risk factor for endothelial dysfunction in pre‐eclampsia

Abstract Pregnancy induces significant changes in the maternal cardiovascular system, and insufficient vascular endothelial adaptations to pregnancy contribute to the development of pregnancy complications such as pre‐eclampsia. Pre‐eclampsia is not only a major cause of maternal morbidity and mortality, but also a significant risk factor for the development of later‐life cardiovascular disease. However, the specific mechanisms underlying the pathophysiology of pre‐eclampsia, as well as the mechanisms for an increased susceptibility to cardiovascular disease later in life, are not fully characterized. In this review, we discuss the concept that excessive pregnancy‐specific dyslipidaemia, particularly hypercholesterolaemia, is a significant risk factor for the development of pre‐eclampsia. We further outline novel potential mechanisms (i.e. oxidized low‐density lipoprotein receptor 1 and toll‐like receptor 4) underlying endothelial dysfunction induced by excessively high cholesterol levels during pregnancy (in the context of pre‐eclampsia), in addition to discussing the overall implications of having had a pregnancy complicated by pre‐eclampsia on later‐life maternal vascular health. Determining the mechanisms by which excessive, pregnancy‐specific dyslipidaemia/hypercholesterolaemia impact maternal endothelial health in pregnancy, and later in life, will create a window of opportunity to diagnose and develop targeted therapy for a susceptible population of women, aiming to ultimately reduce the societal burden of cardiovascular disease. image