Gestational Diabetes Leads to Cardiovascular Vulnerability in Offspring

妊娠期糖尿病导致后代心血管脆弱

• 批准号: 7298841
• 负责人: SANJIV KAUL
• 金额: $ 18.29万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7298841
• 关键词: 3-Dimensional; Adolescence; Adult; Age; Arterial Fatty Streak; Atherosclerosis; Behavior; Blood Glucose; Blood Vessels; Blood Viscosity; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Cell Cycle; Characteristics; Condition; Contrast echocardiography procedure; Coronary Arteriosclerosis; Coronary artery; Depressed mood; Development; Diabetes Mellitus; Diabetic mother; Diet; Disease; Eating; Environment; Erythrocytes; Fatty Liver; Fatty acid glycerol esters; Female; Fetus; Genes; Gestational Diabetes; Glucose; Glycerol; Goals; Growth; Growth and Development function; Health; Histopathology; Hormonal; Human; Hyperlipidemia; Hypertension; Infant; Infiltration; Inflammation; Inflammatory; Insulin; Insulin Resistance; Intracellular Accumulation of Lipids; Kidney; Lead; Leukocytes; Life; Link; Lipids; Measures; Metabolic; Metabolic Marker; Metabolic stress; Metabolism; Microbubbles; Modeling; Monkeys; Morphology; Mothers; Muscle Cells; Myocardial; Myocardium; Newborn Infant; Nutrient; Obesity; Outcome; Pathology; Patient currently pregnant; Pattern; Placenta; Plant Roots; Plasma; Play; Pregnancy; Primates; Process; Reactive Oxygen Species; Regulation; Research Personnel; Rheology; Risk Factors; Role; Severities; Spiral Artery of the Endometrium; Standards of Weights and Measures; Stress; Structure; Techniques; Testing; Tissues; Tobacco use; Villous; cell growth; cytokine; diabetic; fetal; fetus cell; hypercholesterolemia; indexing; intimal medial thickening; intravenous glucose tolerance test; non-diabetic; postnatal; programs; size

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.

心血管疾病是发达国家的首要死因，而动脉粥样硬化是导致死亡的主要原因 导致大多数心血管疾病的过程。通常与动脉粥样硬化相关的危险因素 与成人生活相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 梅利图斯。宫内生活期间开始并在青春期发挥作用的因素也发挥着重要作用 在心血管疾病的发展中。大卫·巴克（David Barker）和他的同事们表现出了强大的实力 胎儿和早期出生生长以及冠状动脉疾病的发展之间的关系。产妇 肥胖、高胆固醇血症、高脂血症和糖尿病可能是关键因素 后代动脉粥样硬化发展中的病理生理作用。了解链接 母体代谢状态和后代代谢状态之间的关系对于理解至关重要 成人心血管疾病的胎儿起源。在这个项目中，我们将研究妊娠糖尿病模型 在随意吃高脂肪饮食的猴子中。这些母猴产生了胰岛素抵抗，并且它们的 后代表现出代谢应激的迹象，包括高血浆甘油和脂肪肝。这将是第一个 对妊娠糖尿病灵长类动物模型心血管系统的研究。我们的总体假设是 心血管系统将遭受代谢异常的不利影响。在胎儿和 对于高脂肪饮食母亲的婴儿，我们将研究1）脉管系统和胎盘的病理变化， 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。我们预计在以下条件下母胎相互作用 代谢应激代表了人类胎儿和新生儿应激的模型。我们期待新的 在此模型中将发现有关冠状动脉疾病根源的信息。