Adiponectin and Endothelial Dysfunction in Adolescents

青少年脂联素和内皮功能障碍

• 批准号: 7886752
• 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/7886752
• 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; 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准备埃德蒙P.威克姆111，医学博士，作为一名独立的临床研究者，专注于传统和非传统的心血管危险因素在超重和肥胖青少年经常出现的血管功能障碍中的作用。 候选人寻求联合收割机，他在儿科，内科和内分泌学的独特培训，以检查脂联素多聚体，循环祖细胞数量和功能，以及青少年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。他将整合这种课堂培训与完成一个多学科的研究协议的指导下，导师的多元化团队，每个具有特殊的研究和培训记录。 拟议的研究将检验以下假设：在青少年中，脂联素（特别强调高分子量[HMW]亚型）部分通过其对循环祖细胞（CPC）数量和功能的影响而导致内皮功能障碍。为了验证这一假设，候选人将测量传统的心血管危险因素（血压、腰围、血脂、血糖）、胰岛素抵抗（使用口服葡萄糖耐量试验期间的葡萄糖和胰岛素值）、炎性细胞因子、脂联素多聚体、CPC数（通过流式细胞术测定的CD 34+细胞）和肱动脉的流动介导的扩张（FMD）在30名正常体重、30名超重和100名11-18岁的肥胖青少年中。基线测量将在60名肥胖青少年中重复进行，这些青少年参加了12周的以家庭为基础的结构化体重管理计划。此外，将对从30名患有代谢综合征（MetS）的肥胖青少年（14-18岁）和30名正常体重儿童中分离的细胞进行体外CPC研究（在小管形成试验期间定量集落形成单位[CFU Hill]和CPC掺入）。最后，在20名青少年（10名肥胖-MetS，10名正常体重）的亚组中，将在存在人重组脂联素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。 公共卫生关系：肥胖青少年患糖尿病、胆固醇升高和血压升高等重大健康问题的风险增加;每种疾病都与心血管疾病风险增加有关。脂联素是脂肪细胞释放的一种激素，可能在最终导致心脏病的早期血管变化中起重要作用。