Mechanisms for Vascular Disease in Women - Inflammation in Pre-eclampsia and Atherosclerosis, 2015

Pre-eclampsia (PE) is a major cause of maternal disease/death in pregnancy and affects about 5% of pregnant women. In severe cases, PE may also involve the fetus, causing premature deliveries and fetal growth restriction. Enhanced systemic inflammation and vascular endothelial activation are characteristic findings in pre-eclamptic women. Similar hallmarks are found in cardiovascular disease (CVD), and in accordance with this; women with previous pre-eclamptic pregnancies, have doubled risk for later-life CVD. In many ways pregnancy may be considered a metabolic stress test and PE may be the first clinical manifestation. This suggests that apparently healthy young women have abnormal metabolic/inflammatory responses. In this project, mechanisms underlying PE and CVD were explored by focusing on inflammation. Both initiating signals (endogenous damage/danger signals and pathogen components) and receptivity (pattern recognition receptors (PRRs)) of cases and controls were investigated. The genetic influence was assessed by genotyping PRR-related genes in women with and without PE in Norwegian cohorts, including the HUNT study. The role of local inflammatory responses at the maternal-fetal site was studied in placental and decidual tissues and in vitro studies of fetal trophoblasts. The aim was to study and compare inflammatory mechanisms associated with both PE and CVD in women. Findings may potentially open for tests for risk assessment, useful for a maternity care aiming to increase attention to pregnant women at risk. Development of CVD appears to have gender-specific mechanisms, which remain to be elucidated. Knowledge gained from the combined study of PE and CVD may generate useful insight in mechanisms underlying the female way of developing CVD.