The goal of this proposal is to investigate the association between the independent risk factor for atherosclerosis, homocysteine, and the pregnancy-specific vascular syndrome preeclampsia. Preeclampsia is the leading cause of maternal mortality in developed countries, increases perinatal mortality five fold and is associated with an increased risk of cardiovascular disease in later life. These studies will be performed to determine total homocysteine concentrations in normal and preeclamptic pregnancies, and this data will be correlated to known markers of oxidative stress which are postulated to play a role in the pathogenesis of preeclampsia. Furthermore, the nutritional and genetic factors responsible for increased homocysteine will be analyzed to determine the mechanisms leading to hyperhomocysteinemia. Lastly, the effect(s) of hyperhomocystienemia upon the functional modifications of the vasculature in pregnancy will be investigated with the use of a hyperhomocysteinemic transgenic mouse model. This study is designed to determine if the vasculature possess a unique sensitivity to the atherogenic molecule, homocysteine, during pregnancy. These studies may potentially identify a common risk factor for preeclampsia, and more importantly may lead to nutritional modifications to reduce the incidence of preeclampsia, similar to results obtained with nutritional modification in subsets of atherosclerotic patients.
