Adiponectin and Endothelial Dysfunction in Adolescents

青少年脂联素和内皮功能障碍

基本信息

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
项目类别：
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

项目摘要

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，M.D。做好准备，成为一名独立的临床研究者，专注于在超重和肥胖青少年中经常出现的血管功能障碍中传统和非传统心血管危险因素的作用。候选人试图结合他在儿科，内科和内分泌学方面的独特培训，以检查脂联素多聚体之间的关系，循环祖细胞的数量和功能以及青少年的内皮功能。候选人将完成研究设计，生物统计学和公共卫生的正式教学培训，从而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，将此课堂培训与完成多学科研究协议结合在一起，每个研究方案都有卓越的研究和培训记录。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，部分原因是其对循环祖细胞（CPC）数量和功能的影响。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（在口腔葡萄糖耐受性测试中使用葡萄糖和胰岛素值），炎性细胞因子，脂质细胞动物，脂连链蛋白多聚体，CPC数字（CD34+ CYTSID）（CD34+ CYTOMD）（FLOW）和流cytome（Frow）（Frow）（Frow）（Flof）（Frow）） 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。在参加基于家庭的，结构化的体重管理计划的12周之后，将在60名肥胖青少年中重复基线措施。此外，将对从30个肥胖青少年（14-18岁）与代谢综合征（MetS）和30个正常人儿童分离的细胞进行体外CPC研究（在小管形成测定过程中的菌落形成单元[CFUHILL]和CPC掺入）。最后，在20个青少年（10个肥胖 - 仪，10个正常体重）的子集中，将在人类重组脂联素的存在下进行第二个小管形成测定，以确定脂联素对CPC功能的影响。公共卫生相关性：肥胖的青少年面临糖尿病，胆固醇升高和升高血压在内的重大健康问题的风险；每种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，在早期血管变化中可能起重要作用，最终导致心脏病。