Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction
Abstract Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF statu...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43363-3 |
| _version_ | 1797452080078651392 |
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| author | Emily S. Lau Athar Roshandelpoor Shahrooz Zarbafian Dongyu Wang James S. Guseh Norrina Allen Vinithra Varadarajan Matthew Nayor Ravi V. Shah Joao A. C. Lima Sanjiv J. Shah Bing Yu Mona Alotaibi Susan Cheng Mohit Jain Gregory D. Lewis Jennifer E. Ho |
| author_facet | Emily S. Lau Athar Roshandelpoor Shahrooz Zarbafian Dongyu Wang James S. Guseh Norrina Allen Vinithra Varadarajan Matthew Nayor Ravi V. Shah Joao A. C. Lima Sanjiv J. Shah Bing Yu Mona Alotaibi Susan Cheng Mohit Jain Gregory D. Lewis Jennifer E. Ho |
| author_sort | Emily S. Lau |
| collection | DOAJ |
| description | Abstract Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention. |
| first_indexed | 2024-03-09T15:03:36Z |
| format | Article |
| id | doaj.art-07f73b5e0093461e99f48c002b887e3d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T15:03:36Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-07f73b5e0093461e99f48c002b887e3d2023-11-26T13:45:10ZengNature PortfolioNature Communications2041-17232023-11-0114111310.1038/s41467-023-43363-3Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fractionEmily S. Lau0Athar Roshandelpoor1Shahrooz Zarbafian2Dongyu Wang3James S. Guseh4Norrina Allen5Vinithra Varadarajan6Matthew Nayor7Ravi V. Shah8Joao A. C. Lima9Sanjiv J. Shah10Bing Yu11Mona Alotaibi12Susan Cheng13Mohit Jain14Gregory D. Lewis15Jennifer E. Ho16Division of Cardiology, Department of Medicine, Massachusetts General HospitalCardioVascular Institute, Division of Cardiology, Department of Medicine, 330 Brookline Avenue, Beth Israel Deaconess Medical CenterDivision of Cardiology, Department of Medicine, Massachusetts General HospitalCardioVascular Institute, Division of Cardiology, Department of Medicine, 330 Brookline Avenue, Beth Israel Deaconess Medical CenterDivision of Cardiology, Department of Medicine, Massachusetts General HospitalDepartment of Preventive Medicine, Northwestern University Feinberg School of MedicineDivision of Cardiology, Department of Medicine Johns Hopkins University School of MedicineCardiology Division, Boston University School of MedicineVanderbilt Clinical and Translational Research Center (VTRACC), Vanderbilt University Medical CenterDivision of Cardiology, Department of Medicine Johns Hopkins University School of MedicineDivision of Cardiology, Department of Medicine, Northwestern University Feinberg School of MedicineDepartment of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health School of Public HealthDivision of Pulmonary and Critical Care and Sleep Medicine, University of California San DiegoDepartment of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical CenterDepartment of Medicine and Department of Pharmacology, University of California San DiegoDivision of Cardiology, Department of Medicine, Massachusetts General HospitalCardiovascular Research Center, Massachusetts General HospitalAbstract Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention.https://doi.org/10.1038/s41467-023-43363-3 |
| spellingShingle | Emily S. Lau Athar Roshandelpoor Shahrooz Zarbafian Dongyu Wang James S. Guseh Norrina Allen Vinithra Varadarajan Matthew Nayor Ravi V. Shah Joao A. C. Lima Sanjiv J. Shah Bing Yu Mona Alotaibi Susan Cheng Mohit Jain Gregory D. Lewis Jennifer E. Ho Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction Nature Communications |
| title | Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction |
| title_full | Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction |
| title_fullStr | Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction |
| title_full_unstemmed | Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction |
| title_short | Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction |
| title_sort | eicosanoid and eicosanoid related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction |
| url | https://doi.org/10.1038/s41467-023-43363-3 |
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