ELEVATED HOMOCYSTEINE AS A RISK FACTOR FOR PREECLAMPSIA

本提案的目的是调查 动脉粥样硬化的独立危险因素，同型半胱氨酸， 妊娠特异性血管综合征先兆子痫。 先兆子痫是 发达国家产妇死亡率的主要原因， 围产期死亡率是五倍，并与增加的风险有关。 晚年的心血管疾病 这些研究将用于 测定正常人和先兆子痫患者的总同型半胱氨酸浓度 怀孕，这些数据将与已知的标志物相关， 氧化应激被假定在发病机制中起作用 先兆子痫 此外，营养和遗传因素 将分析导致同型半胱氨酸增加的原因，以确定 导致高同型半胱氨酸血症的机制。 最后，影响（S） 高同型半胱氨酸血症后的功能修改的 在怀孕期间的脉管系统将被调查与使用 高同型半胱氨酸血症转基因小鼠模型。 本研究设计 为了确定脉管系统是否对血管系统的运动具有独特的敏感性， 动脉粥样硬化分子，同型半胱氨酸，在怀孕期间。 这些研究 可能潜在地确定先兆子痫的一个共同危险因素， 重要的是可能导致营养调整，以减少发病率 先兆子痫，类似于营养调整获得的结果 在动脉粥样硬化患者的亚群中。

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.