Aortic Dilatation in Endurance Athletes: A Physiologic and Mechanistic Study

项目摘要/摘要 这位候选人最近加入了马萨诸塞州综合医院(MGH)心血管专科的工作人员 绩效计划(CPP)，一个独特的组织，其目标包括进行一流的人类健康和 性能研究。CPP的核心使命是以耐力运动员为榜样，通过 研究运动对心血管系统的影响。本提案将这一框架应用于评估 详细介绍了运动对大动脉的影响。 这一建议源于双重观察，即a)运动训练的心肌适应是一种 公认的过程，被认为是适应性的，而不是病理的，而主动脉的可塑性则不是 有文献记载，以及b)耐力运动员合并主动脉增大在临床上很常见。 练习一下。因此，候选人进行了一项初步研究，招募了约450名运动员，并记录了 与已建立的人群标准相比，这一人群中主动脉扩张的患病率升高。这 研究提案旨在定义自然历史、潜在的生理学和潜在的潜在机制 耐力运动员的这种主动脉扩张的表型，首要目标是帮助确定 这可能代表了一种运动相关的适应，而不是一种新的过度使用病理形式。 为了实现这些目标，申请人建议在其先前工作的基础上，利用大量的 他招募的运动员参加了最初的研究。对运动员受试者进行纵向跟踪 用超声心动图反映评价指标。一个子集将经历详细的比较 心肺运动试验的生理表型，先进的超声心动图技术 包括对心内和主动脉血流模式的非侵入性评估，血管功能分析，以及 使用计算机断层扫描进行详细的解剖成像。在可能的情况下，测试将在休息时和在 对生理刺激的反应。表型图谱将被比较有无运动员 主动脉扩张和对照受试者的主动脉扩张以评估生理差异和潜力 机械装置。分子评价的重点将放在血浆微小RNA(MiRNA)，这类分子具有良好的生物相容性。 已确定的运动反应性和已知的与主动脉疾病和循环疾病的机制关联 在锻炼之前和之后，将对这些组的miRNA图谱进行评估。 应聘者的职业发展计划包括运动生理学、心脏和心脏方面的高级培训 成像和生理表型、翻译科学和研究方法，所有这些都在 一个独特的多学科团队的导师。提出的科学科学将为未来奠定基础 评估这一人群的临床结果的研究，并整合额外的运动翻译研究- 相关的主动脉疾病，这将构成候选人未来R01提案的基础。在整个过程中 在获得K23奖项后，候选人的目标是发展成为一名独立的临床和翻译研究员。

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.