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FRIMED2-FRIPRO forskerprosjekt, medisin og helse

The BRIDGE study: Bridging pregnancy and fetal microchimerism with longterm female maternal cardiovascular and neurovascular health

Alternative title: BRIDGE: Broen mellom fosterceller fra svangerskapet i mors blod og risikoen for fremtidig hjerte- og karsydom, inkludert hjernehelse

Awarded: NOK 12.0 mill.

Cardiovascular disease (CVD), including stroke, is a leading cause of premature death and disability in women, and is expected to increase substantially in years to come. The BRIDGE study aims to fill the knowledge gap surrounding CVD in women, and to identify new targets for early prevention and precision medicine. One risk factor for CVD that only affects women is having a pregnancy with a dysfunctional placenta. Examples of placental dysfunction include preeclampsia and fetal growth restriction. Recent studies show that preeclampsia also increases the risk of acquiring long-lived, fetal stem cell-like cells. The resulting phenomenon, in which fetal cells are incorporated into the woman’s body, is termed fetal microchimerism. Our hypothesis is that placental dysfunction plays a role in increasing transfer of these fetal cells to the mother. Our novel proposal is that exposure to these cells, promotes inflammation and disease of small and large arteries over time. This may trigger changes in how the cells of the arteries read and translate genes to produce proteins. So-called epigenetic alterations are likely key to the development of atherosclerosis and CVD. In our study, we plan to count the number of fetal cells present in maternal blood samples and biopsies from the walls of maternal arteries in two groups. In a group of elderly women with or without a risk of stroke, we will study the arteries feeding into the brain. In a group of women giving birth, we will study the arteries feeding into the placenta. We will compare our findings to vascular wall biomarkers, and to arterial imaging- and clinical characteristics. We have a strong team of interdisciplinary collaborators and comprehensive biobanks made up of biological material from women during and after pregnancy, and from older women with or without stroke, creating a unique platform for in-depth study of CVD and underlying mechanisms.

Cardiovascular disease (CVD), including ischemic stroke, is a leading cause of premature death and disability in women, and is expected to increase substantially. We aim to fill in the knowledge gap for female CVD, and to identify new targets for early prevention. One sex-specific risk factor for CVD in women is previous pregnancies complicated by placental dysfunction, e.g. preeclampsia and fetal growth restriction. It has recently been shown that preeclampsia also confers an increased risk of acquiring long-living, stem cell-like cells from the fetus. This phenomenon is termed fetal microchimerism (FMC). Our hypothesis is that placental dysfunction mediates an increased transfer of fetal cells to the mother. Our original proposal is that increased FMC exposure to the woman’s cardiovasculature promotes generalized arterial inflammation and disease of small and large arteries, potentially triggering epigenetic alterations. Epigenetic alterations are likely key to the pathogenesis of atherosclerosis and CVD, translating environmental factors, including pregnancy-related factors, into disease development, and represent potential therapeutic targets Benefitting from our available comprehensive research biobanks with extensive clinical phenotyping data, we will quantify FMC in maternal blood and in the wall of uteroplacental and carotid arteries, both at delivery and in older women with, or at risk of, ischemic stroke. FMC findings will be compared to vascular wall epigenetic biomarkers, and to artery imaging- and clinical phenotypes. Our strong team of transdisciplinary collaborators, combined with comprehensive biobanks comprising extensive pregnancy-, postpartum-, and stroke populations, create a unique platform for in-depth study of underlying mechanisms. We aim to fill in the knowledge gap for female CVD and to facilitate future precision medicine with targeted prophylaxis started at a young age to optimize female cardiovascular health.

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FRIMED2-FRIPRO forskerprosjekt, medisin og helse