Metabolism, Skeletal Muscle, Cardiac Disease, Exercise

新陈代谢、骨骼肌、心脏病、运动

基本信息

批准号：
7589768
负责人：
JOHN P KONHILAS
金额：
$ 12.01万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7589768
关键词：
Address Aerobic Exercise Animals Award Biometry Cardiac Cardiovascular Physiology Characteristics Citrate (si)-Synthase Clinical Congestive Heart Failure Coupled Creatine Kinase Development Plans Disease Disease Progression Doctor of Philosophy Environment Enzymes Exercise Exertion Fatigue Fatty Acids Fiber Funding Genetic Goals Heart Diseases Hypertrophic Cardiomyopathy Journals Ligands Link Lipoproteins Measures Mediator of activation protein Mentors Metabolic Metabolism Mitochondria Modeling Molecular Mus Muscle Fibers Muscle Weakness Myocardial Infarction Myosin Heavy Chains Nonesterified Fatty Acids PPAR alpha Pathway interactions Patients Peroxisome Proliferator-Activated Receptors Phenotype Physiology Postdoctoral Fellow Process Protein Isoforms Recombinants Recovery Regulation Regulator Genes Research Role Running Scientist Site Skeletal Muscle Staining method Stains Structure Techniques Technology Testing Tetrazolium Time Training Training Activity Transgenes Transgenic Animals Transgenic Organisms Translational Research Triglycerides Viral activating transcription factor adeno-associated viral vector biological systems career career development clinically significant cytochrome c oxidase experience human disease lipoprotein lipase meetings mutant oxidation programs recombinase skills

项目摘要

DESCRIPTION (provided by applicant): Candidate: The candidate, John P. Konhilas, Ph.D., is a research associate endeavoring to broaden his extensive training in cardiovascular physiology to encompass additional biological systems and timely molecular techniques. Dr. Konhilas1 immediate career goal is to acquire the research and professional skills necessary for achieving his long-term goal of developing an independent, extramurally-funded translational research program focusing on the regulation of skeletal muscle characteristics during cardiac disease states and exercise in animals as it relates to human disease. The proposed K01 development plan will provide Dr. Konhilas with the additional experience and training to achieve this goal. Career Development Plan: Training activities during the award period include, (1) acquiring new and refining present research skills, (2) structured activities including coursework in scientific integrity, biostatistics, and attendance/presentation at journal clubs, scientific meetings, and mentoring interactions. Environment: Dr. Konhilas has assembled a team of mentors to provide guidance in every facet of the proposal. The sponsor, Dr. Leslie Leinwand, is a well-established extramurally funded scientist and a proven mentor. She has provided a productive and nurturing research environment necessary for career development. Research: The hypothesis to be tested states that the oxidative capacity of skeletal muscle is reduced during cardiac disease states and can be recovered by exercise training. To examine the role of critical metabolic mediators in this process, lipoprotein lipase or peroxisome proliferator-activated receptor alpha will be genetically disrupted in skeletal muscle by systemic administration of adeno-associated viral (AAV) vectors at specific times during cardiac disease progression and exercise. In all animals, the skeletal muscles will be analyzed for MyHC content, muscle fiber size, and oxidative capacity. Relevance: Severe skeletal muscle weakness and fatigue upon exertion are major clinical features that occur in patients with congestive heart failure (CHF). The exercise intolerance can be reversed in CHF patients with aerobic exercise independent of central cardiac effects. Therefore, it is of major clinical significance that the mechanistic link be determined between cardiac disease, the associated abnormalities in skeletal muscle, and exercise. This proposal will examine specific regulators of this disease process and evaluate their role during disease and exercise recovery.

描述（由申请人提供）：候选人：候选人约翰·康希拉斯（John P. Konhilas）博士是一名研究助理，努力扩大他在心血管生理学方面的广泛培训，以涵盖其他生物系统和及时的分子技术。 Konhilas1博士的直接职业目标是获得他的长期目标，即建立一个独立的，外部资助的翻译研究计划所必需的研究和专业技能，重点是调节心脏疾病期间骨骼肌特征的调节，并在动物中与人类疾病有关。拟议的K01开发计划将为Konhilas博士提供额外的经验和培训，以实现这一目标。职业发展计划：奖励期间的培训活动包括，（1）获得新的和精炼的当前研究技能，（2）结构化活动，包括在科学完整性，生物统计学方面的课程，在期刊俱乐部的出勤/演讲，科学会议和指导互动。环境：Konhilas博士已经组建了一组导师，以在提案的各个方面提供指导。赞助商莱斯利·莱因万德（Leslie Leinwand）博士是一位成熟的外部资助科学家，也是一位经过验证的导师。她为职业发展提供了一种富有成效的研究环境。研究：要测试的假设指出，在心脏病状态下，骨骼肌的氧化能力降低，可以通过运动训练来恢复。为了检查关键代谢介质在这一过程中的作用，脂蛋白脂肪酶或过氧化物酶体增殖物激活的受体α将在骨骼肌中通过全身性施用在心脏病进展和运动过程中的特定时间中腺相关病毒（AAV）载体在骨骼肌中受到遗传破坏。在所有动物中，将分析骨骼肌的MYHC含量，肌肉纤维大小和氧化能力。相关性：劳累时严重的骨骼肌无力和疲劳是充血性心力衰竭（CHF）患者发生的主要临床特征。在CHF患者中，有氧运动与心脏中心作用无关。因此，确定心脏疾病，骨骼肌的相关异常和运动之间的机理联系是至关重要的临床意义。该提案将检查该疾病过程的特定调节因子，并评估其在疾病和行使康复中的作用。