Mentoring in Patient-Oriented and Translational HFpEF Research

项目摘要/摘要 心力衰竭(HF)是世界范围内的一个主要公共健康问题，有一半的心衰患者患有 保存(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的病因和影响因素以及临床异质性的了解有限 亚型。候选人研究工作的中心目标是使用临床和转化性研究 更好地了解人类HFpEF及其亚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症的作用，肥胖症被认为是诱导系统性促肥胖的因素。 炎症状态，进而导致心血管功能障碍和重塑，导致HFpEF。 应聘者是一名心力衰竭心脏病专家，专注于HFpEF的研究，并有一项长期的跟踪 成功辅导的记录。目前的工作包括一项多队列努力，以检查上游监管机构 HFpEF的全身性炎症。这一点得到了一项正在进行的前瞻性研究的补充，该研究考察了 肥胖症和胰岛素抵抗与HFpEF相关的肺动脉高压。这个项目的首要目标是 提案的目的是为候选人提供关键的长期支持，以使正在进行的削减 临床和行政承诺，并为对临床感兴趣的学员扩大培训机会 以及以患者为中心的转化性心力衰竭研究。此应用程序将支持候选人创建 独特的培训机会，通过利用持续资助的努力，实现新的以患者为导向的研究 被辅导者。在目标1中，我们将研究HFpEF炎症特征的性别差异，以便更好地 了解为什么患有HFpEF的男性和女性表现出不同的疾病表型。在目标2中，我们将研究 肥胖和代谢功能障碍是右心功能的决定因素，是 HFpEF的结果。候选人的多学科研究计划中的这些研究机会， 再加上马萨诸塞州综合医院充满活力的科学社区和广泛的教育资源 医院和哈佛大学将为学员寻求职业生涯创造无与伦比的环境 以病人为中心的研究。最终，我们希望这项建议将支持发展和指导 心力衰竭研究中的新临床研究人员，并为未来重点研究奠定基础 HFpEF中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.