Grant: Project Grant

Conditions during pregnancy can have long-term effects on the health of mothers and babies. Pregnant women who have high blood pressure and their urine contains protein are said to suffer from pre-eclampsia. Women and babies afflicted by pre-eclampsia have a higher chance of getting heart disease later in life. Babies with low birth weight (LBW) also have increased risk of heart disease later in life. Interestingly, excessive inflammation in pregnancy is linked to pre-eclampsia and LBW. We want to determine if and how abnormal inflammation in pregnancy increases the risk of subsequent heart disease in mothers and their children. To accomplish these goals, we developed a rat model of pre-eclampsia and LBW. In this model, inflammation in pregnant rats is induced by administration of a bacterial substance called lipopolysaccharide (LPS). Rats injected with LPS develop a condition similar to pre-eclampsia and their pups have LBW. We plan to monitor these rats and their pups after delivery to look for signs of increased risk of cardiovascular disease. We previously found that certain anti-inflammatory agents and exercise prevent inflammation and LBW induced by LPS. Therefore we will conduct studies to determine if exercise or treatment with anti-inflammatory agents mitigates risk of disease. Higher risk of disease in women and children who suffer from pre-eclampsia and LBW is linked to modifications in the DNA structure or in DNA-associated proteins. These modifications are called 'epigenetic alterations'. We plan to determine if inflammation in pregnancy leads to epigenetic alterations that could predict disease later in life. For this, we plan to use our rat model as well as blood samples from women and babies collected at the time of delivery. Our proposed studies are important because, if exercise and anti-inflammatories reduce the risk of disease in pregnant women and their children, this could lay the groundwork for to new treatments to prevent heart disease.