Adiponectin and Endothelial Dysfunction in Adolescents

青少年脂联素和内皮功能障碍

• 批准号: 7662117
• 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/7662117
• 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; Life Style; Lipids; Master of Public Health; Measures; Mediating; Mentors; Metabolic; Metabolic syndrome; Metabolism; Modality; Modification; 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为Edmond P.Wickham 111医学博士作为一名独立临床调查员的富有成效的职业生涯做好准备，专注于传统和非传统心血管风险因素在超重和肥胖青少年常见的血管功能障碍中的作用。这位候选人寻求将他在儿科、内科和内分泌学方面的独特培训结合起来，研究青少年脂联素多聚体、循环祖细胞数量和功能以及内皮功能之间的关系。应聘者将完成研究设计、生物统计学和公共卫生方面的正式教学培训，最终获得公共卫生硕士学位。他将在一个不同的导师团队的指导下，将这种课堂培训与完成多学科研究方案结合起来，每个导师团队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]亚型)有助于内皮功能障碍，部分是通过其对循环祖细胞(CPC)数量和功能的影响。为了验证这一假设，应试者将测量30名正常体重、30名超重和100名肥胖青少年的传统心血管危险因素(血压、腰围、血脂、血糖)、胰岛素抵抗(使用口服葡萄糖耐量测试中的血糖和胰岛素值)、炎症细胞因子、脂联素多聚体、CPC数量(CD34+细胞通过流式细胞仪测定)以及肱动脉血流介导的扩张(FMD)。在参与以家庭为基础的结构化体重管理计划12周后，将对60名肥胖青少年重复基线测量。此外，从30名患有代谢综合征的肥胖青少年(14-18岁)和30名正常体重的儿童分离的细胞将进行体外CPC研究(克隆形成单位量化[CFUHill]和在小管形成试验中CPC掺入)。最后，在20名青少年(10名肥胖蛋氨酸，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。 公共卫生相关性：肥胖青少年患重大健康问题的风险增加，包括糖尿病、胆固醇升高和血压升高；每一种疾病都与心血管疾病的风险增加有关。脂联素是一种由脂肪细胞释放的激素，可能在最终导致心脏病的早期血管变化中发挥重要作用。