ELEVATED HOMOCYSTEINE AS A RISK FACTOR FOR PREECLAMPSIA

这项提案的目标是调查 动脉粥样硬化的独立危险因素、同型半胱氨酸和 妊娠特异性血管综合征先兆子痫。先兆子痫是 发达国家孕产妇死亡的主要原因，增加 围产儿死亡率是对照组的五倍，并与增加的风险有关 晚年的心血管疾病。这些研究将被用于 正常和先兆子痫患者血清总同型半胱氨酸浓度的测定 怀孕，这一数据将与已知的 被认为在发病机制中发挥作用的氧化应激 先兆子痫的症状。此外，营养和遗传因素 将对同型半胱氨酸增加负责的人进行分析以确定 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对心脏功能的影响 妊娠期间的血管系统将通过使用 高同型半胱氨酸血症转基因小鼠模型。这项研究是设计的 以确定血管系统是否对 导致动脉粥样硬化的分子同型半胱氨酸，在怀孕期间。这些研究 可能会确定先兆子痫的共同危险因素，以及更多 重要的是，可能会导致营养修改，以减少发病率 先兆子痫，类似于营养改良的结果 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.