Mentoring in Patient-Oriented and Translational HFpEF Research

以患者为导向的转化性 HFpEF 研究的指导

• 批准号: 10040036
• 负责人: Jennifer E Ho
• 金额: $ 12.35万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10040036
• 关键词: Address; Adverse event; Affect; Analytical Chemistry; Area; Attention; Award; Biochemical; Bioinformatics; Blood Vessels; Cardiopulmonary; Cardiopulmonary Physiology; Cardiovascular system; Classification; Clinical; Clinical Investigator; Clinical Research; Clostridium perfringens epsilon toxin; Collaborations; Communities; Complement; Complex; Coupled; Coupling; Development; EFRAC; Environment; Exercise; Exercise Physiology; Exercise Test; Fellowship Program; Foundations; Functional disorder; Funding; Future; General Hospitals; Goals; Heart; Heart failure; Hospitals; Human; Individual; Inflammation; Inflammatory; Inflammatory Response; Infrastructure; Insulin Resistance; Interdisciplinary Study; International; Investigation; Knowledge; Laboratories; Lead; Learning; Link; Lung; Massachusetts; Medicine; Mentors; Mentorship; Metabolic Diseases; Metabolic dysfunction; Mid-Career Clinical Scientist Award (K24); Monitor; Morbidity - disease rate; Obesity; Organ; Outcome; Pathogenesis; Pathway interactions; Patients; Phenotype; Physiological; Prevention therapy; Productivity; Prospective Studies; Public Health; Public Health Schools; Pulmonary Hypertension; Research; Research Methodology; Research Personnel; Research Support; Research Training; Resources; Right Ventricular Function; Risk Factors; Role; Sampling; Seminal; Sex Differences; Therapeutic; Training; Translational Research; United States National Institutes of Health; Universities; Ventricular; Woman; Work; adjudicate; base; cardiometabolism; career; career development; clinical epidemiology; clinical heterogeneity; cohort; disease phenotype; disorder prevention; education resources; effective therapy; hemodynamics; interest; men; mortality; optimal treatments; outcome prediction; patient oriented; patient oriented research; preservation; programs; prospective; public health relevance; recruit; training opportunity; translational research program; translational study

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.

项目摘要/摘要 心力衰竭（HF）是全球一个主要的公共卫生问题，有一半的HF患者有 保留（HFPEF），而不是减少射血分数。但是，HFPEF仍然是一个治疗挑战， 鉴于当前对HFPEF内因果关系和促成因素以及临床异质性的了解有限 亚表征。候选人研究工作的核心目标是使用临床和翻译研究 更好地理解人类HFPEF及其亚表征的机制和贡献者的方法。一 专注于实验室是为了研究肥胖的作用，这被认为会引起系统性的影响 炎症状态表明，进而驱动心血管功能障碍并重塑导致HFPEF。 候选人是心力衰竭心脏病专家，研究重点是HFPEF和一条长期的曲目 成功指导的记录。当前的工作包括一项多核心努力，以检查 HFPEF的全身炎症。这是一项前瞻性的研究，研究了这一点 HFPEF相关肺动脉高压中的肥胖和胰岛素抵抗。总体目标 提案将为候选人提供至关重要的长期支持，以使持续减少 临床和行政承诺，并为对临床感兴趣的受训者扩大培训机会 和转化为患者的心力衰竭研究。此应用程序将支持候选人创建 通过利用持续资助的努力来实现新的面向患者的研究LED的独特培训机会 由受训者。在AIM 1中，我们将调查HFPEF炎症性特征的性别差异，以便更好 了解为什么患有HFPEF的男人和女性显示出不同的疾病表型。在AIM 2中，我们将检查 肥胖和代谢功能障碍是右心室功能的决定因素，这是一个重要的预测指标 HFPEF的结果。候选人的多学科研究计划中的这些研究机会， 加上马萨诸塞州一般的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从事职业的学员创造一个无与伦比的环境 面向患者的研究。最终，我们希望该建议将支持 心力衰竭研究的新临床研究者，并为未来的研究奠定了基础 HFPEF中的疾病预防和最佳疗法。