GESTATIONAL DIABETES LEADS TO CARDIOVASCULAR VULNERABILITY IN OFFSPRING

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 越来越多的证据表明，异常的母体代谢状态会对胎儿的心血管系统产生有害的影响，这种影响可能会持续一辈子。例如，妊娠期糖尿病可能会导致母体代谢状态的改变，其特征是血浆营养浓度异常、细胞因子水平升高和促氧化剂水平升高。随之而来的是胎盘结构和功能异常以及胎盘代谢功能异常。因此，母亲的状态对胎儿来说是一种代谢压力。我们发现，怀孕的雌性猴子如果长期食用高饱和脂肪的饮食数年，就会患上妊娠期胰岛素抵抗。母亲新陈代谢健康状况不佳和饮食习惯不佳共同导致后代面临广泛的健康风险。这些研究的目的是使用NHP模型来调查母亲的健康和饮食对后代心血管系统发育的影响。这些研究的特点是：1)胎盘和心血管系统的病理变化；2)子代几个发育阶段的心血管功能；3)幼年子代的微血管功能。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.