Adiponectin and Endothelial Dysfunction in Adolescents

青少年脂联素和内皮功能障碍

• 批准号: 8298573
• 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/8298573
• 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; 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; Instruction; 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; 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; receptor; repaired; research and development; waist circumference; young adult

The proposed K23 career development and research plans will prepare EdmondP. Wickham 111, M.D., for a productive career as an independent clinicalinvestigator focusing on the role of traditional andnon-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 publichealth 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 molecularweight [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 insulinvalues during an oral glucose tolerance test), inflammatory cytokines,adiponectin multimers, CPC number (CD34+ cells determined by flow cytometry), and flow-mediateddilation (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 (quantificationof colony forming units [CFU- Hill] 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 beperformed in the presence of human recombinant adiponectin to determine the effects of adiponectin on CPCfunction. RELEVANCE (See instructions): 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.

拟议的K23职业发展和研究计划将准备Edmondp。威克汉姆111，医学博士 作为独立临床评估者的生产力，专注于传统和诺顿传统的角色 在超重和肥胖的青少年中，血管功能障碍中的心血管危险因素经常存在。 候选人试图将他在儿科，内科和内分泌学方面的独特培训结合到 检查脂联素多聚体，循环祖细胞的数量和功能之间的关系，以及 青少年的内皮功能。候选人将完成研究设计方面的正式教学培训， 生物统计学和Publichealth导致公共卫生硕士学位。他将整合这个教室 在多元化团队的指导下完成多学科研究方案的培训 导师，每个人都有出色的研究和培训记录。 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]同工型）有助于内皮功能障碍，部分通过其对 循环祖细胞（CPC）编号和功能。为了检验这一假设，候选人将测量 传统的心血管危险因素（血压，腰围，脂质，葡萄糖），胰岛素抵抗 （在口服葡萄糖耐受性测试期间使用葡萄糖和胰岛素），炎性细胞因子，脂联素 多聚体，CPC数（CD34+细胞由流式细胞仪确定），以及流动介导的（FMD） 30个正常体重，30个超重和100名肥胖青少年11-18岁的肱动脉。基线度量 在参加基于家庭的，结构化的12周之后，将在60名肥胖青少年中重复 体重管理计划。此外，体外CPC研究（定量形成单元的定量[CFU- 小管形成期间的山丘]和CPC掺入）将在从30个肥胖的细胞上进行 患有代谢综合征（MetS）和30名正常重量儿童的青少年（14-18岁）。最后，在一个 20个青少年（10个肥胖仪，10个正常重量）的子集，第二个小管形成测定 在人类重组脂联素存在下，以确定脂联素对CPCFunction的影响。 相关性（请参阅说明）： 肥胖的青少年的风险增加了，包括糖尿病在内的重大健康问题 麦芽脂，胆固醇升高和血压升高；每个都与增加有关 心血管疾病的风险。脂联素是一种由脂肪细胞释放的激素，在 早期血管最终导致心脏病。