Adiponectin and Endothelial Dysfunction in Adolescents

青少年脂联素和内皮功能障碍

• 批准号: 8094275
• 负责人: Edmond Pryce Wickham
• 金额: $ 13.46万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-10 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8094275
• 关键词: Address; Adipocytes; Adipose tissue; Adolescent; Adult; Affect; Age; Anti-Inflammatory Agents; Anti-inflammatory; Antiatherogenic; Atherosclerosis; Attenuated; Behavior Therapy; Biological Assay; Biometry; Blood Pressure; Blood Vessels; Bone Marrow; CD34 gene; Cardiovascular Diseases; Cell Count; Cell physiology; Cells; Child; Cholesterol; Clinical Investigator; Colony-forming units; Complex; Development; Diabetes Mellitus; Doctor of Medicine; Dyslipidemias; Endocrine Glands; Endocrinology; Endothelial Cells; Epidemic; Exposure to; Family; Flow Cytometry; Foam Cells; Functional disorder; Glucose; Health; Heart Diseases; Hematopoietic stem cells; Hormones; Human; Hyperlipidemia; Hypertension; Impaired fasting glycaemia; In Vitro; Inflammatory; Insulin; Insulin Resistance; Internal Medicine; Intervention; Lead; Lipids; Master of Public Health; Measures; Mediating; Mentors; Metabolic; Metabolic syndrome; Metabolism; Modality; Molecular Weight; Nitric Oxide; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Overweight; Pathway interactions; Pediatrics; Peptides; Platelet Activation; Play; Prevalence; Principal Investigator; Production; Property; Protein Isoforms; Protocols documentation; Public Health; Recombinants; Records; Reporting; Research; Research Design; Research Training; Risk; Role; Serum; Stem cells; Structure; Testing; Training; Umbilical vein; Vasodilation; Weight; Weight Gain; Weight maintenance regimen; adipokines; adiponectin; angiogenesis; base; brachial artery; cardiovascular disorder risk; cardiovascular risk factor; career; career development; cell transformation; cytokine; diabetic; experience; good diet; high risk; improved; macrophage; next generation; novel; precursor cell; premature; prevent; programs; public health relevance; receptor; repaired; research and development; waist circumference; young adult

DESCRIPTION (provided by applicant): The proposed K23 career development and research plans will prepare Edmond P. Wickham 111, M.D., for a productive career as an independent clinical investigator focusing on the role of traditional and non-traditional cardiovascular risk factors in the vascular dysfunction frequently present in overweight and obese adolescents. The candidate seeks to combine his unique training in Pediatrics, Internal Medicine, and Endocrinology to examine the relationships among adiponectin multimers, circulating progenitor cell number and function, and endothelial function in adolescents. The candidate will complete formal didactic training in study design, biostatistics, and public health resulting in a Masters of Public Health degree. He will integrate this classroom training with the completion of a multi-disciplinary research protocol under the guidance of a diverse team of mentors, each with exceptional research and training records. The proposed studies will test the hypothesis that in adolescents, adiponectin (with particular emphasis on the high molecular weight [HMW] isoform) contributes to endothelial dysfunction, in part through its effects on circulating progenitor cell (CPC) number and function. To test this hypothesis, the candidate will measure traditional cardiovascular risk factors (blood pressure, waist circumference, lipids, glucose), insulin resistance (using glucose and insulin values during an oral glucose tolerance test), inflammatory cytokines, adiponectin multimers, CPC number (CD34+ cells determined by flow cytometry), and flow-mediated dilation (FMD) of the brachial artery in 30 normal-weight, 30 overweight, and 100 obese adolescents ages 11-18. Baseline measures will be repeated in 60 of the obese adolescents after 12-weeks of participation in a family-based, structured weight management program. Additionally, in vitro CPC studies (quantification of colony forming units [CFUHill] and CPC incorporation during a tubule formation assay) will be performed on cells isolated from 30 obese adolescents (ages 14-18) with the metabolic syndrome (MetS) and 30 normal-weight children. Finally, in a subset of 20 adolescents (10 obese-MetS, 10 normal-weight), a second tubule formation assay will be performed in the presence of human recombinant adiponectin to determine the effects of adiponectin on CPC function. PUBLIC HEALTH RELEVANCE: Obese adolescents are at increased risk of developing significant health problems including diabetes mellitus, elevated cholesterol, and elevated blood pressure; each of which is associated with an increased risk of cardiovascular disease. Adiponectin, a hormone released by fat cells, may play an important role in the early blood vessel changes that ultimately lead to heart disease.

描述（由申请人提供）：拟议的K23职业发展和研究计划将使Edmond P. Wickham 111, m.d.成为一名独立的临床研究者，专注于传统和非传统心血管危险因素在超重和肥胖青少年中常见的血管功能障碍中的作用。该候选人寻求结合他在儿科，内科和内分泌学方面的独特培训，研究青少年中脂联素多聚体，循环祖细胞数量和功能以及内皮功能之间的关系。候选人将完成研究设计、生物统计学和公共卫生方面的正式教学培训，获得公共卫生硕士学位。他将在多元化的导师团队的指导下，将课堂培训与多学科研究协议的完成结合起来，每位导师都有出色的研究和培训记录。这些研究将验证以下假设：在青少年中，脂联素（特别是高分子量[HMW]异构体）通过影响循环祖细胞（CPC）的数量和功能而导致内皮功能障碍。为了验证这一假设，候选人将测量30名体重正常、30名超重和100名年龄在11-18岁的肥胖青少年的传统心血管危险因素（血压、腰围、血脂、葡萄糖）、胰岛素抵抗（在口服葡萄糖耐量试验中使用葡萄糖和胰岛素值）、炎症因子、脂联素多聚体、CPC数（通过流式细胞术测定的CD34+细胞）和肱动脉血流介导扩张（FMD）。60名肥胖青少年在参加了一个以家庭为基础的、有组织的体重管理项目12周后，将重复基线测量。此外，体外CPC研究（集落形成单位的量化[CFUHill]和小管形成试验中的CPC结合）将对30名患有代谢综合征（MetS）的肥胖青少年（14-18岁）和30名体重正常的儿童分离的细胞进行。最后，在20名青少年（10名肥胖- mets， 10名正常体重）中，将在人重组脂联素存在的情况下进行第二次小管形成试验，以确定脂联素对CPC功能的影响。