Gestational Diabetes Leads to Cardiovascular Vulnerability in Offspring

在发达国家，心血管疾病是导致死亡的主要原因，而动脉粥样硬化是导致死亡的主要原因

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.