Mechanisms of Vascular Dysfunction in Obesity & the Metabolic Syndrome

描述(由申请人提供)： 候选人：在儿科心脏病学研究员期间，我与Bogalusa心脏研究研究员一起工作，并计划继续临床/研究结合的职业生涯，但我执业中的人员变动导致临床工作量增加，挫败了我完成公共卫生硕士学位的努力。我的目标是成为一名儿科心血管疾病流行病学的独立研究员，但没有实现。当有机会加入辛辛那提儿童医院时，我接受了挑战，渴望让我的职业生涯重回正轨。这项K23奖项将有助于为我提供成为儿科血管功能专家所需的培训。 环境：儿童环境是我回归研究事业的理想环境。我减少的临床职责现在集中在预防心脏病学上，我在辛辛那提大学攻读硕士课程。我得到了最新的血管设备和无数的指导机会，这导致了富有成效的跨学科关系，最终形成了两个摘要的试点数据，并准备了这份K23提案。 研究：美国儿童肥胖症急剧增加，这些儿童面临靶器官损伤、成人糖尿病、心脏病和中风的风险。肥胖导致靶器官损害的途径之一可能涉及脂肪来源的脂联素(APN)对血管功能的影响。APN直接保护血管系统，在肥胖、与其相关的炎症和冠状动脉疾病中减少。低水平与胰岛素抵抗和代谢综合征的血脂异常有关。我们建议对学龄儿童进行一项横断面研究，研究肥胖和血管功能之间的关系，以确定功能障碍的机制是否与心血管危险因素、炎症和APN的异常水平有关。臂动脉扩张性、体重指数、血压、血脂、C反应蛋白和APN将在正在进行的普林斯顿地标研究(N=2000)中进行测量。队列样本(n=450)也将接受臂部血流介导的扩张、增大指数和脉搏波速度。将在正常、肥胖和肥胖胰岛素抵抗受试者之间进行实验室和血管测量对比。将比较成熟的和新的非侵入性血管功能检测方法。 相关性：显示与超重相关的代谢异常会导致儿童血管功能障碍，这将有助于医生识别高危儿童进行早期治疗，以防止未来的心脏病发作和中风。

DESCRIPTION (provided by applicant): Candidate: During Pediatric Cardiology fellowship, I worked with Bogalusa Heart Study investigators and planned to continue a combined clinical/research career but personnel changes in my practice led to an increased clinical load frustrating my attempts to complete a Masters in Public Health. My goal of becoming an independent researcher in Pediatric CV disease epidemiology was left unfulfilled. When the chance came to join Cincinnati Children's Hospital, I embraced the challenge, eager to get my career back on track. This K23 award will be instrumental in providing me with the training I need to become an expert in Pediatric Vascular Function. Environment: Children's is the ideal environment for my transition back to a research career. My reduced clinical duties now focus on Preventive Cardiology, and I am enrolled in the Masters program at the University of Cincinnati. I have been provided up-to-date vascular equipment and numerous mentoring opportunities which have led to productive interdisciplinary relationships culminating in pilot data for 2 abstracts and in preparation of this K23 proposal. Research: Childhood obesity has increased dramatically in the U.S., and these children are at risk for target organ damage, adult diabetes, heart disease and stroke. One of the pathways by which obesity induces target organ damage may involve fat derived adiponectin's (APN) effect on vascular function. APN directly protects the vasculature and is reduced in obesity, its related inflammation and in coronary artery disease. Low levels are associated with insulin resistance and the dyslipidemia of metabolic syndrome. We propose a cross-sectional study of school-aged adolescents to study relationships between obesity and vascular function to determine if the mechanisms of dysfunction may relate to abnormal levels of CV risk factors, inflammation and APN. Brachial Artery Distensibility, BMI, BP, lipids, CRP, and APN will be measured in the ongoing Princeton Landmark Study (N=2000). A cohort sample (n=450) will also undergo brachial flow mediated dilatation, augmentation index and pulse wave velocity. Contrasts in laboratory & vascular measures will be made among normals, obese and obese-insulin-resistant subjects. Well-established and newer non-invasive methods of vascular function testing will be compared. Relevance: Showing that metabolic abnormalities related to overweight lead to blood vessel dysfunction in children will help doctors identify high-risk children for early treatment to prevent future heart attack and stroke.