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

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.