Mentoring in Patient-Oriented and Translational HFpEF Research

项目总结/摘要 心力衰竭（HF）是世界范围内的主要公共卫生问题，并且呈现HF的患者中有一半患有心力衰竭。 保留（HFpEF），而不是减少射血分数。然而，HFpEF仍然是一个治疗挑战， 鉴于目前对HFpEF的因果和影响因素以及临床异质性的了解有限 亚表型候选人研究工作的中心目标是利用临床和转化研究 更好地理解人类HFpEF及其亚表型的机制和贡献者的方法。一 实验室的重点一直是研究肥胖的作用，肥胖被认为会引起全身性的促衰老， 炎症状态，其反过来驱动心血管功能障碍和重塑，导致HFpEF。 候选人是一名心力衰竭心脏病专家，研究重点是HFpEF和长期跟踪 成功的指导记录。目前的工作包括一个多队列的努力，检查上游监管机构， HFpEF中的全身性炎症。作为补充，正在进行一项前瞻性研究， 肥胖和胰岛素抵抗与HFpEF相关的肺动脉高压。本项目的总体目标是 建议是为候选人提供关键的长期支持，使其能够从 临床和行政承诺，并扩大对临床感兴趣的学员的培训机会 和转化的以病人为导向的心力衰竭研究。此应用程序将支持候选人创建 独特的培训机会，通过利用正在进行的资助工作，使新的以患者为导向的研究， 被mentees。在目的1中，我们将研究HFpEF中炎症特征的性别差异，以便更好地研究HFpEF中的炎症特征。 了解为什么男性和女性HFpEF显示不同的疾病表型。在目标2中，我们将研究 肥胖和代谢功能障碍是右心室功能的决定因素， HFpEF的结果。这些研究机会在候选人的多学科研究计划， 再加上马萨诸塞州综合医院充满活力的科学界和广泛的教育资源， 医院和哈佛大学将为学员创造一个无与伦比的环境， 以病人为中心的研究。最终，我们希望这项提案将支持以下方面的发展和指导： 心力衰竭研究的新临床研究者，并为未来的研究奠定基础，重点是 HFpEF的疾病预防和最佳治疗。

Project Summary/Abstract Heart failure (HF) is a major public health problem worldwide, and half of patients presenting with HF have preserved (HFpEF), rather than reduced ejection fraction. However, HFpEF remains a therapeutic challenge, given current limited understanding of causal and contributing factors, and clinical heterogeneity within HFpEF subphenotypes. The central goal of the candidate's research work is to use clinical and translational research approaches to better understand mechanisms and contributors to human HFpEF and its subphenotypes. One focus in the laboratory has been to study the role of obesity, which is thought to induce a systemic pro- inflammatory state that, in turn, drives cardiovascular dysfunction and remodeling leading to HFpEF. The candidate is a heart failure cardiologist with a research focus on HFpEF and a long-standing track record of successful mentoring. Current work includes a multi-cohort effort to examine upstream regulators of systemic inflammation in HFpEF. This is complemented by a prospective ongoing study examining the role of obesity and insulin-resistance in HFpEF-associated pulmonary hypertension. The overarching goals of this proposal are to provide the candidate with the crucial long-term support to enable the ongoing reduction from clinical and administrative commitments, and to expand training opportunities for mentees interested in clinical and translational patient-oriented heart failure research. This application will support the candidate in creating unique training opportunities by leveraging ongoing funded efforts to enable new patient-oriented studies led by mentees. In Aim 1, we will investigate sex differences in inflammatory profiles in HFpEF in order to better understand why men and women with HFpEF display distinct disease phenotypes. In Aim 2, we will examine obesity and metabolic dysfunction as determinants of right ventricular function, an important predictor of outcomes in HFpEF. These research opportunities within the candidate's multidisciplinary research program, coupled with a vibrant scientific community and extensive educational resources at Massachusetts General Hospital and Harvard University will create an unparalleled environment for trainees pursuing a career in patient-oriented research. Ultimately, we hope this proposal will support the development and mentoring of new clinical investigators in heart failure research, and lay the foundation for future investigations focused on disease prevention and optimal therapies in HFpEF.