Cardiolipin Biosynthesis and Mitochondrial Energy Production in Pediatric Idiopathic Dilated Cardiomyopathy

小儿特发性扩张型心肌病的心磷脂生物合成和线粒体能量产生

基本信息

批准号：
8869753
负责人：
Kathryn C. Chatfield
金额：
$ 13.07万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-05 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8869753
关键词：
Address Adolescent Adrenergic Agonists Adult Anabolism Animal Model Appearance Area Basic Science Biochemical Biogenesis Biological Assay Biology Cardiac Cardiolipins Cardiology Cardiovascular Physiology Cardiovascular system Carnitine Carnitine Palmitoyltransferase I Child Childhood Citrate (si)-Synthase Clinical Clinical Sciences Colorado Complex Data Diagnosis Diet Dilated Cardiomyopathy Disease Disease Outcome Doctor of Philosophy Electron Microscopy Electron Transport Electron Transport Complex III Energy Metabolism Ensure Environment Enzymes Etiology Fatty Acids Fellowship Free Radical Formation Functional disorder Funding Genetic Goals Healthcare Healthcare Systems Heart Heart Transplantation Heart failure Human Impairment Isoproterenol Life Linoleic Acids Mediator of activation protein Medical Mentors Mentorship Mitochondria Modeling Molecular Mus Myocardial Myocardial tissue Myocardium Omega-6 Fatty Acids Organelles Outcome Oxidative Stress Pathology Pathway interactions Pattern Pediatric Hospitals Pediatrics Performance Philadelphia Phospholipids Physicians Primary idiopathic dilated cardiomyopathy Principal Investigator Process Production Program Development Regulation Research Residencies Resources Role Sampling Scientist Side Stress Subgroup System Therapeutic Intervention Tissue Banking Tissue Banks Tissues Training Training Programs Translating Transplanted tissue Universities Up-Regulation Vulnerable Populations Work base career cost human tissue improved interest long chain fatty acid member mitochondrial dysfunction novel oxidation pediatric department pediatric patients programs public health relevance research study response success therapeutic target transcription factor translational medicine

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in the field pediatric heart failure. The principal investigator has MD, Ph.D. training, completed clinical residency training in Pediatrics and Genetics at the Children's Hospital of Philadelphia, and recently completed fellowship training in Pediatric Cardiology at the University of Colorado. During this period of clinical training she has developed an interest in the etiologies of heart failure (HF) in children, and initiated a research program under the primary mentorship of Dr. Brian Stauffer. The proposed research program will be the first to provide a thorough characterization of mitochondrial function and energy metabolism in pediatric idiopathic dilated cardiomyopathy (IDC). The project addresses a critical healthcare disparity in an under-represented and vulnerable population: children who have received little benefit from advances in adult HF treatments. The goal of the work is to impact outcomes of heart failure in children through identification of unique pathophysiologic processes in myocardium of children with IDC, allowing identification of dietary and pharmacologic therapies tailored to pediatric disease. The mentorship team provides a diverse training backgrounds and research expertise in cardiovascular biology. Each member is extramurally funded, a leader in the field of pediatric heart failure and cardiovascular physiology, and committed to their role as research mentors. Preliminary work has demonstrated evidence of changes in mitochondrial content, phospholipid content, and energy capacity in pediatric IDC. This research will focus on further characterization of mitochondrial dysfunction through analysis of stress and biogenesis responses and direct assay of the electron transport chain and mediators of fatty-acid influx for ß-oxidation using human tissue. Features of pediatric HF are recapitulated by treatment of a juvenile mouse with isoproterenol (ISO). This model is proposed as a model to further delineate the mechanisms of altered mitochondrial energy utilization in pediatric HF. The Department of Pediatrics at the University of Colorado Denver provides an ideal setting for training physician-scientists by incorporating expertise and resources from Clinical and Basic Science Departments throughout the University of Colorado System. This environment, with access to a large human heart tissue bank and the principal investigator's mentorship team are ideally suited to ensure the success of a novel area of research upon which a career in translational medicine can be constructed.

描述（由申请人提供）：该提案描述了C型心力衰竭的5年培训计划。费城医院，以及最近的Comphia，在这段临床培训期间对儿童心力衰竭（HF）的病因产生了兴趣，并开始了一项研究在布莱恩·斯塔夫（Brian Stauffer）博士的主要指导下。儿童心肌的病理生理学允许对小儿疾病的饮食和药物治疗在应力和压力的应力和直接的ron转运链和脂肪酸 - 脂肪 - 氧化的介体进行β-氧化的介体的情况下，该模型的进一步表征。科罗拉多州的小儿培训和基础科学部门的培训理想的培训环境，改变了丹佛的小儿小儿的小儿利用。为了确保新颖的edicine研究领域。