Eicosanoid Profiles as Determinants of HFpEF

类二十烷酸分布作为 HFpEF 的决定因素

• 批准号: 10543612
• 负责人: Jennifer E Ho
• 金额: $ 11.6万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10543612
• 关键词: Eicosanoid; Profiles; Determinants; HFpEF

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. Comorbidities such as obesity and hypertension are thought to induce a systemic pro- inflammatory state that, in turn, drives cardiovascular dysfunction and remodeling leading to HFpEF. Indeed, downstream markers of inflammation have been observed in HFpEF. However, accumulating evidence suggests that upstream mediators of inflammation are more likely to play a causal role in disease pathogenesis and, in turn, serve as effective therapeutic targets. Upstream initiation of inflammation in humans is governed primarily by small molecule effectors of arachidonic acid metabolism, termed eicosanoids. These bioactive lipids include thromboxanes, prostaglandins, lipoxins, and leukotrienes, and harbor pro- and anti-inflammatory activity, vasoactivity, and direct modulation of cardiomyocyte signaling and contractile function. To date, the interaction between eicosanoid pathways and development of HFpEF remain poorly understood, thus limiting our ability to harness their therapeutic potential. Advanced methods using mass spectrometry now allow for the rapid and accurate quantification of >150 upstream eicosanoid mediators representing multiple enzymatic origins. To provide a more detailed understanding of how upstream eicosanoid pathways may underlie the progression from risk factors to HFpEF, and shed light onto HFpEF subphenotypes, we will pursue two related lines of investigation: In Aim 1, we will investigate the association of circulating eicosanoids with clinical risk factors, subclinical cardiac remodeling, and incident HFpEF in the community. In Aim 2, we will examine the association of eicosanoid profiles with HFpEF subphenotypes, including distinct cardiac and extracardiac vascular dysfunction among clinical HFpEF patients. This proposal leverages a unique multidisciplinary team of collaborators with expertise in clinical epidemiology, advanced imaging, exercise physiology, bioinformatics, analytical chemistry, and lipidomics. Our systematic approach to comprehensively investigating the components of upstream inflammatory activity in two large, well-phenotyped community-based cohorts, complemented by a group of clinical HFpEF patients with comprehensive exercise hemodynamic evaluations and deep physiologic phenotyping to assess distinct aspects of cardiovascular dysfunction, promises to yield important insights into the molecular determinants of HFpEF. Importantly, these studies will lay the foundation for future investigations focused on disease prevention and optimal therapies tailored to HFpEF subphenotype.

项目总结/文摘

项目成果

Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study.

• DOI: 10.1161/jaha.122.029980
• 发表时间: 2023-11-07
• 期刊: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• 影响因子: 5.4
• 作者: Shah, Ravi V.;Hwang, Shih-Jen;Murthy, Venkatesh L.;Zhao, Shilin;Tanriverdi, Kahraman;Gajjar, Priya;Duarte, Kevin;Schoenike, Mark;Farrell, Robyn;Brooks, Liana C.;Gopal, Deepa M.;Ho, Jennifer E.;Girerd, Nicholas;Vasan, Ramachandran S.;Levy, Daniel;Freedman, Jane E.;Lewis, Gregory D.;Nayor, Matthew
• 通讯作者: Nayor, Matthew

Deep learning to estimate cardiac magnetic resonance-derived left ventricular mass.

• DOI: 10.1016/j.cvdhj.2021.03.001
• 发表时间: 2021-04
• 期刊: Cardiovascular digital health journal
• 作者: Khurshid S;Friedman SF;Pirruccello JP;Di Achille P;Diamant N;Anderson CD;Ellinor PT;Batra P;Ho JE;Philippakis AA;Lubitz SA
• 通讯作者: Lubitz SA

Unmasking Nonpreserved Heart Structure, Function, and Energetics in Heart Failure With Preserved Ejection Fraction With Magnetic Resonance Imaging Coupled With Exercise.

通过磁共振成像结合运动，揭示保留射血分数的心力衰竭中未保留的心脏结构、功能和能量。

• DOI: 10.1161/circulationaha.121.056974
• 发表时间: 2021
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Ho,JenniferE;Nguyen,Christopher;Lewis,GregoryD
• 通讯作者: Lewis,GregoryD

The role of obesity in inflammatory markers in COVID-19 patients.

• DOI: 10.1016/j.orcp.2020.12.004
• 发表时间: 2021-01
• 期刊: Obesity research & clinical practice
• 影响因子: 4.3
• 作者: McNeill JN;Lau ES;Paniagua SM;Liu EE;Wang JK;Bassett IV;Selvaggi CA;Lubitz SA;Foulkes AS;Ho JE
• 通讯作者: Ho JE

Deep learning on resting electrocardiogram to identify impaired heart rate recovery.

• DOI: 10.1016/j.cvdhj.2022.06.001
• 发表时间: 2022-08
• 期刊: CARDIOVASCULAR DIGITAL HEALTH JOURNAL
• 作者: Diamant, Nathaniel;Di Achille, Paolo;Weng, Lu-Chen;Lau, Emily S.;Khurshid, Shaan;Friedman, Samuel;Reeder, Christopher;Singh, Pulkit;Wang, Xin;Sarma, Gopal;Ghadessi, Mercedeh;Mielke, Johanna;Elci, Eren;Kryukov, Ivan;Eilken, Hanna M.;Derix, Andrea;Ellinor, Patrick T.;Anderson, Christopher D.;Philippakis, Anthony A.;Batra, Puneet;Lubitz, Steven A.;Ho, Jennifer E.
• 通讯作者: Ho, Jennifer E.