GESTATIONAL DIABETES LEADS TO CARDIOVASCULAR VULNERABILITY IN OFFSPRING

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 越来越多的证据表明，异常的母亲代谢状态会对胎儿的心血管系统产生有害影响，这种影响可能会持续一生。 例如，妊娠糖尿病可能会导致母体代谢状态改变，其特征是血浆营养浓度异常、细胞因子水平和促氧化剂水平升高。随之而来的是胎盘结构和功能的异常以及胎盘代谢功能的异常。 因此，母亲的状态对胎儿来说是一种代谢压力。我们发现，如果怀孕的雌性猴子多年来长期食用高饱和脂肪的饮食，就会出现妊娠胰岛素抵抗。 母亲代谢健康状况不佳和饮食习惯相结合，会导致后代面临广泛的健康风险。 这些研究的目的是利用NHP模型来研究母亲健康和饮食对后代心血管系统发育的影响。 这些研究将表征：1）胎盘和心血管系统的病理变化，2）后代在几个发育阶段的心血管功能，以及3）幼年后代的微血管功能。 这些研究将有助于确定食用高脂肪饮食的动物后代未来患心血管疾病的风险。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. There is increasing evidence that abnormal maternal metabolic status exerts deleterious effects on the cardiovascular system of the fetus that may last for a lifetime. Gestational diabetes, for example, may lead to an altered maternal metabolic state characterized by abnormal plasma nutrient concentrations, increased cytokine levels and pro-oxidant profile. Abnormal placental structure and function and abnormal metabolic function of the placenta then follow. Thus the state of the mother becomes a metabolic stress to the fetus. We have discovered that pregnant female monkeys acquire gestational insulin resistance if they chronically consume a diet high in saturated fats for several years. The combination of poor maternal metabolic health and diet contribute to a broad range of health risks in the offspring. The purpose of these studies is to use the NHP model to investigate the effects maternal health and diet on the development of the cardiovascular system in the offspring. These studies will characterize: 1) pathological changes in the placenta and cardiovascular systems, 2) the cardiovascular function of the offspring at several developmental stages, and 3) microvascular function in juvenile offspring. These studies will help determine the future risk of cardiovascular disease for offspring of animals consuming a high fat diet.