Prof. Ilona Hromadnikova, Charles University, Third Faculty of Medicine; Dr Katerina Kotlabova, Charles University, Third Faculty of Medicine; Lenka Dvorakova, Charles University, Third Faculty of Medicine; Dr Jan Sirc, Institute for the Care of Mother and Child and Charles University, Third Faculty of Medicine ; Prof. Ladislav Krofta, Institute for the Care of Mother and Child and Charles University, Third Faculty of Medicine
Charles University Innovations Prague s.r.o.
Epigenetic changes characteristic for cardiovascular/cerebrovascular diseases are present in women and children with a history of pregnancy-related complications. Screening of cardiovascular/cerebrovascular disease associated microRNAs may be used to identify women and children at a higher risk of later development of cardiovascular/cerebrovascular diseases. We demonstrate that pregnancy-related complications induce postpartum/postnatal alterations in gene expression of cardiovascular/cerebrovascular disease-associated microRNAs. Screening for those disease-associated microRNAs may be used to identify women and children with a history of pregnancy-related complications at a higher risk of later developing cardiovascular/cerebrovascular diseases.
The expression profile of microRNAs was assessed using real-time RT-PCR in whole peripheral blood samples of 275 women and 309 children (age 3 to 11 years) postpartum/postnatally, compared between groups with a history of gestational hypertension (GH), preeclampsia (PE), fetal growth restriction (FGR) and controls. The results show a correlation between the severity of the disease with respect to clinical signs, delivery date, and Doppler parameters. In addition, the expression profile of microRNAs in children was analyzed in relation to the current presence of cardiovascular risk factors (overweight/obesity and/or prehypertension/hypertension) and cardiovascular complications (valve problems and heart defects). Both individual cardiovascular/cerebrovascular disease associated microRNAs and combined screening of microRNA biomarkers showed the highest accuracy to identify women and children at a higher risk of developing a cardiovascular/cerebrovascular disease later in life. At 90.0% specificity, particular microRNAs were able to identify as much as 33.33% of women and 47.83% of children at a higher risk, who might benefit from the implementation of early preventive strategies. Any epigenetic changes that were induced by pregnancy-related complications are long-acting (up-regulation of some microRNAs was also observed in placental tissues or umbilical cord blood) and may predispose children affected with GH, PE or FGR to later development of cardiovascular/cerebrovascular diseases. Novel epigenetic changes (aberrant expression profile of microRNAs) also appeared in a proportion of children that were exposed to GH, PE or FGR.
Stakeholders like state and private health care providers, national institutes of health and medical research, the scientific audience may be potentially interested in the utilization of the method to assess cardiovascular risk in women and children with a history of pregnancy-related complications. Alternatively, for pharma or biotechnology companies it could be interesting to develop a novel commercial diagnostic/prognostic kit to easier assess cardiovascular risk in women and children with prior exposure to pregnancy-related complications.
preclinic - 275 mothers, 309 children tested so far
Czech patent application PV-2018-595
Czech patent application PV 2018-597