Gestational Diabetes Leads to Cardiovascular Vulnerability in Offspring

心血管疾病是发达国家的主要死亡原因，动脉粥样硬化是 对大多数心血管疾病负有责任的过程。动脉粥样硬化的危险因素通常与 成人生活包括高血压、吸烟、肥胖、高胆固醇血症、高脂血症和糖尿病 糖尿病。开始于宫内生活并持续到青春期的因素也起着重要作用。 在心血管疾病的发展中起重要作用。大卫·巴克和他的同事们向人们展示了 胎儿和早期出生发育与冠心病发生的关系母性 肥胖、高胆固醇血症、高脂血症和糖尿病可能是起关键作用的因素 子代动脉粥样硬化形成过程中的病理生理学作用。了解链接 母体的代谢状态和子代的代谢状态之间的关系对于理解 成人心血管疾病的胎儿起源。在这个项目中，我们将研究妊娠期糖尿病的模型 在随意食用高脂肪饮食的猴子身上。这些母猴对胰岛素产生抵抗力，它们的 后代表现出代谢压力的迹象，包括高血浆甘油和脂肪肝。这将是第一次 妊娠期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 新陈代谢异常会对心血管系统造成不利影响。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，以及4)心脏功能的变化 心肌细胞的生长。我们预计在以下条件下的母胎相互作用 代谢应激是人类胎儿和新生儿应激的一种模型。我们期待着新的 关于冠状动脉疾病根源的信息将在这个模型中被发现。

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.