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为EdmondP做准备。威克姆111，医学博士，用于 作为一名独立的临床研究者，专注于传统和非传统的作用， 血管功能障碍中的心血管危险因素经常出现在超重和肥胖青少年中。 候选人寻求联合收割机结合他在儿科，内科和内分泌学的独特培训， 检查脂联素多聚体、循环祖细胞数量和功能之间的关系， 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， 生物统计学和公共卫生导致公共卫生硕士学位。他将把这间教室 培训与完成一个多学科的研究协议的指导下，一个多元化的团队， 导师，每个人都有出色的研究和培训记录。 拟议的研究将检验这样的假设，即在青少年中，脂联素（特别强调 高分子量[HMW]同种型）部分地通过其对内皮细胞的作用而导致内皮功能障碍。 循环祖细胞（CPC）的数量和功能。为了验证这一假设，候选人将测量 传统心血管危险因素（血压、腰围、血脂、血糖）、胰岛素抵抗 （在口服葡萄糖耐量试验期间使用葡萄糖和胰岛素值），炎性细胞因子，脂联素 多聚体，CPC数量（通过流式细胞术测定的CD 34+细胞），以及细胞的流动介导的扩张（FMD）。 肱动脉在30正常体重，30超重，和100肥胖青少年年龄11-18。基线措施 将在60名肥胖青少年中重复进行， 体重管理计划。此外，体外CPC研究（定量菌落形成单位[CFU- Hill]和在小管形成测定期间CPC掺入）将对从30个肥胖小鼠中分离的细胞进行 患有代谢综合征（MetS）的青少年（14-18岁）和30名正常体重的儿童。最后，在一 20名青少年（10名肥胖-MetS，10名正常体重）的亚组，将进行第二次小管形成测定 在存在人重组脂联素的情况下测定脂联素对CPC功能的影响。 相关性（参见说明）： 肥胖青少年患糖尿病等重大健康问题的风险增加 糖尿病、胆固醇升高和血压升高;其中每一种都与增加的 心血管疾病风险。脂联素是脂肪细胞释放的一种激素， 早期的血管变化最终导致心脏病。