Gestational Diabetes Leads to Cardiovascular Vulnerability in Offspring

心血管疾病是发达国家死亡的主要原因， 心血管疾病的发病机制。动脉粥样硬化的危险因素 与成年生活有关的疾病包括高血压、吸烟、肥胖、高胆固醇血症、高脂血症和糖尿病 糖尿病。在宫内生活期间开始并在青春期起作用的因素也起重要作用 心血管疾病的发展。大卫巴克和他的同事们展示了 胎儿和纳塔尔早期生长与冠状动脉疾病发展之间的关系。产妇 肥胖、高胆固醇血症、高脂血症和糖尿病可能是 在后代动脉粥样硬化发展中的病理生理作用。了解链接 母亲的代谢状态和后代的代谢状态之间的联系对于理解 成人心血管疾病的胎儿起源。在这个项目中，我们将研究一个妊娠糖尿病模型 在随意吃高脂肪食物的猴子身上。这些母猴变得胰岛素抵抗， 后代表现出代谢应激的迹象，包括高血浆甘油和脂肪肝。这将是第一 妊娠糖尿病灵长类动物模型的心血管系统研究。我们的总体假设是 心血管系统将遭受代谢异常的有害影响。在胎儿和 高脂饮食母亲的婴儿，我们将研究1）血管和胎盘的病理变化， 2)心血管功能的变化，3）心肌微血管行为的变化，4） 心肌细胞的生长。我们预期在以下条件下母胎的相互作用 代谢应激代表人类胎儿和新生儿应激的模型。我们期待新的 在该模型中将发现关于冠状动脉疾病的根源的信息。

ardiovascular disease is the leading cause of death in the developed world and atherosclerosis is the process responsible for most cardiovascular disease. Risk factors for atherosclerosis commonly associated with adult life include hypertension, tobacco use, obesity, hypercholesterolemia, hyperlipidemia and diabetes mellitus. Factors starting during intrauterine life and acting through adolescence also play an important role in the development of cardiovascular disease. David Barker and colleagues have shown the strong relationship between fetal and early natal growth, and the development of coronary artery disease. Maternal obesity, hypercholesterolemia, hyperlipidemia and diabetes mellitus are factors that likely play a key pathophysiological role in the development of atherosclerosis in the offspring. Understanding the link between the maternal metabolic state and the metabolic state of the offspring is essential to understanding the fetal origins of adult cardiovascular disease. In this project, we will study a model of gestational diabetes in monkeys that eat a high fat diet ad libitum. These maternal monkeys become insulin resistant and their offspring show signs of metabolic stress including high plasma glycerol and fatty liver. This will be the first study of the cardiovascular system in a primate model of gestational diabetes. Our overall hypothesis is that the cardiovascular system will suffer detrimental effects of the metabolic abnormalities. In the fetuses and infants of mothers on the high fat diet, we will study 1) the pathological changes in vasculature and placenta, 2) changes in cardiovascular function, 3) changes in myocardial microvascular behavior and, 4) changes in cellular growth of the myocardium. We expect that the maternofetal interactions under conditions of metabolic stress represent a model for fetal and new born stress in humans. We expect that new information on the roots of coronary artery disease will be discovered in this model.