Vascular Dysfunction in Obesity and Metabolic Syndrome

肥胖和代谢综合征中的血管功能障碍

• 批准号: 7023644
• 负责人: Elaine Mott Urbina
• 金额: $ 12.8万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7023644
• 关键词: C reactive protein; adiponectin; adolescence (12-20); angiocardioultrasonography; biomarker; blood flow measurement; blood lipid; blood pressure; blood tests; body composition; cardiovascular disorder epidemiology; cardiovascular disorder risk; clinical research; diabetes risk; echocardiography; human subject; insulin sensitivity /resistance; metabolic syndrome; middle childhood (6-11); obesity; patient oriented research; pulse pressure wave; statistics /biometry

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.

描述（由申请人提供）： 候选人：在儿科心脏病学奖学金期间，我与 Bogalusa 心脏研究研究人员合作，并计划继续临床/研究相结合的职业生涯，但我的实践中的人事变动导致临床负担增加，使我完成公共卫生硕士学位的尝试受挫。我成为小儿心血管疾病流行病学独立研究员的目标未能实现。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。这个 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： 儿童学院是我重返研究生涯的理想环境。我减少的临床职责现在主要集中在预防心脏病学，并且我正在辛辛那提大学攻读硕士学位。我获得了最新的血管设备和大量的指导机会，这促成了富有成效的跨学科关系，最终为 2 个摘要提供了试点数据，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。肥胖引起靶器官损伤的途径之一可能涉及脂肪源性脂联素（APN）对血管功能的影响。 APN 直接保护脉管系统，并在肥胖及其相关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。我们建议对学龄青少年进行一项横断面研究，以研究肥胖与血管功能之间的关系，以确定功能障碍的机制是否可能与心血管危险因素、炎症和 APN 的异常水平有关。正在进行的普林斯顿地标研究 (N=2000) 将测量肱动脉扩张性、BMI、血压、血脂、CRP 和 APN。队列样本 (n=450) 还将经历肱动脉血流介导的扩张、增强指数和脉搏波速度。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的对比。将比较成熟的和更新的无创血管功能测试方法。 相关性：表明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并进行早期治疗，以预防未来的心脏病和中风。