Aortic Dilatation in Endurance Athletes: A Physiologic and Mechanistic Study

耐力运动员的主动脉扩张：生理学和机制研究

基本信息

批准号：
10524299
负责人：
Timothy CHURCHILL
金额：
$ 19.66万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10524299
关键词：
Acute Address Age Aorta Aortic Diseases Area Arteries Biochemical Biological Markers Biology Blood Pressure Blood Vessels Blood flow Body Size Caliber Cardiac Cardiopulmonary Cardiovascular system Chronic Clinical Clinical Investigator Complement Dangerousness Data Development Plans Dilatation - action Dose Echocardiography Enrollment Environment Equilibrium Evaluation Exercise Exercise Physiology Exercise Test Exertion Functional disorder Future General Hospitals General Population Genetic Goals Grant Growth Health Human Hypertension Image Individual Isometric Exercise Isotonic Exercise Massachusetts Mediator of activation protein Mentored Patient-Oriented Research Career Development Award Mentorship MicroRNAs Mission Modeling Molecular Myocardial Natural History Organ Outcome Pathologic Pathology Patients Pattern Performance Persons Phenotype Physical activity Physiological Physiology Plasma Play Population Populations at Risk Positioning Attribute Prevalence Process Publications Regulation Research Research Methodology Research Proposals Rest Risk Risk Factors Role Sampling Science Scientist Sports Strenuous Exercise Structure Surveys Syndrome Techniques Testing Time Tissues Training Translating Translational Research Uncertainty Validation Veterans Work X-Ray Computed Tomography aged anatomic imaging ascending aorta base career career development circulating microRNA clinical practice cohort comparative comparison group endurance exercise exercise training experience follow-up heart imaging high risk population indexing insight male multidisciplinary next generation sequencing novel primary outcome programs prospective response sedentary sex transcriptome sequencing translational scientist translational study

项目摘要

PROJECT SUMMARY / ABSTRACT The candidate recently joined the staff at Massachusetts General Hospital (MGH) in the Cardiovascular Performance Program (CPP), a unique group whose goals include conducting top-caliber human health and performance research. A core mission of the CPP is to use endurance athletes as a model through which to study the impacts of exercise on the cardiovascular system. This proposal applies this framework to evaluate in detail on the impact of exercise on the aorta. This proposal emerged from the dual observations that a) myocardial adaptation to exercise training is a well-established process that is felt to be adaptive rather than pathologic, while plasticity of the aorta has not been documented, and b) endurance athletes with aortic enlargement are commonly encountered in clinical practice. The candidate accordingly performed an initial study enrolling ~450 athletes and documenting an elevated prevalence of aortic dilatation in this population as compared to established population norms. This research proposal aims to define natural history, underlying physiology, and potential mechanisms underlying this phenotype of aortic dilation in endurance athletes, with the overarching goal of helping to establish whether this may represent an exercise-associated adaptation vs a novel form of overuse pathology. To achieve these goals, the applicant proposes to build off his prior work, leveraging the large cohort of athletes whom he enrolled into the initial study. Longitudinal follow-up will be performed on athlete subjects using echocardiography to mirror the index assessment. A subset will undergo detailed comparative physiologic phenotyping with cardiopulmonary exercise testing, advanced echocardiographic techniques including non-invasive evaluation of intracardiac and aortic blood flow patterns, vascular function profiling, and detailed anatomic imaging with computed tomography. Where possible, testing will be performed at rest and in response to physiologic provocation. Phenotypic profiles will be compared across athletes with and without aortic dilatation and control subjects with aortic dilatation to assess physiologic differences and potential mechanisms. Molecular evaluation will focus on plasma microRNA (miRNA), a class of molecules with well- established exercise responsiveness and known mechanistic associations with aortic disease, and circulating miRNA profiles will be assessed across these groups before and after exercise. The candidate’s career development plan includes advanced training in exercise physiology, cardiac imaging and physiologic phenotyping, translational science, and research methodology, all under the mentorship of a unique multidisciplinary team. The proposed science science will set the stage for future studies to assess clinical outcomes in this population and integrate additional translational study of exercise- associated aortic disease, which will form the basis of the candidate’s future R01 proposals. Over the course of the K23 award, the candidate’s goal is to develop into an independent clinical and translational investigator.

项目摘要 /摘要候选人最近加入了马萨诸塞州综合医院（MGH）的工作人员绩效计划（CPP），一个独特的团体，其目标包括进行顶级人类健康和绩效研究。 CPP的核心任务是将耐力运动员用作模型研究运动对心血管系统的影响。该建议应用此框架评估详细介绍运动对主动脉的影响。该提议来自双重观察，即a）心肌适应运动训练是良好的过程被认为是自适应而不是病理的，而主动脉的可塑性却没有被记录在案，b）临床通常会遇到高级扩大的耐力运动员实践。因此，候选人进行了一项初步研究，招收了约450名运动员并记录了与确定的人口规范相比，该人群中主动脉扩张的患病率升高。研究建议旨在定义自然历史，潜在的生理学和潜在机制耐力运动员中主动脉词典的表型，其总体目标是帮助确定是否是否这可以代表与运动相关的适应性，而不是一种新颖的过度使用病理。为了实现这些目标，适用的提案要建立他的先前工作，利用大量队列他参加了初步研究的运动员。纵向随访将对运动员进行使用超声心动图来反映索引评估。子集将进行详细的比较通过心肺运动测试，高级超声心动图技术的生理表型包括对心脏内和主动脉血流模式的非侵入性评估，血管功能分析以及通过计算机断层扫描详细的解剖成像。在可能的情况下，将在休息和中进行测试对生理挑衅的反应。在有和没有的运动员中，将比较表型的轮廓主动脉扩张和控制受试者具有主动脉扩张，以评估生理差异和潜力机制。分子评估将集中于血浆microRNA（miRNA），这是一类具有良好分子的分子建立了运动响应能力和已知的机械性关联与晚期疾病，并循环锻炼前后，将在这些组中评估miRNA谱。候选人的职业发展计划包括运动生理学的高级培训成像和生理表型，转化科学和研究方法，都在独特的多学科团队的遗产。拟议的科学将为未来奠定基础评估该人群中临床结果的研究，并整合了运动的其他翻译研究 - 相关的主动脉疾病将构成候选人未来R01提案的基础。在整个过程中候选人的目标是K23奖，是发展成为独立的临床和翻译研究员。