| Title: | Nicotinamide for the treatment of heart failure with preserved ejection fraction |
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| Authors: | ID Abdellatif, Mahmoud (Author)
ID Herbst, Viktoria (Author)
ID Koser, Franziska (Author)
ID Durand, Sylvère (Author)
ID Adão, Rui (Author)
ID Vasques-Nóvoa, Francisco (Author)
ID Freundt, Johanna K (Author)
ID Voglhuber, Julia (Author)
ID Pricolo, Maria Rosaria (Author)
ID Kasa, Michael (Author)
ID Sedej, Simon (Author), et al. |
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| Files: |  Abdellatif-2021-Nicotinamide_for_the_treatment.pdf (8,23 MB)
MD5: 09AB91CF86C1F6F0B74EFF2B671213EA
 https://www.science.org/doi/10.1126/scitranslmed.abd7064?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
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| Language: | English |
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| Work type: | Scientific work |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | MF - Faculty of Medicine
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| Abstract: | Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD+). Elevating NAD+ by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in Dahl salt-sensitive rats), or cardiometabolic syndrome (in ZSF1 obese rats). This effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium adenosine triphosphatase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD+ precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD+ precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans. |
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| Keywords: | heart failure, hypertension, niacinamide, metabolic syndrome |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 18.07.2020 |
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| Article acceptance date: | 12.01.2021 |
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| Publication date: | 10.02.2021 |
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| Publisher: | American Association for the Advancement of Science |
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| Year of publishing: | 2021 |
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| Number of pages: | Str. 1-15 |
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| Numbering: | Letn. 13, Št. 580 |
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| PID: | 20.500.12556/DKUM-89686  |
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| UDC: | 616.12 |
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| ISSN on article: | 1946-6242 |
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| COBISS.SI-ID: | 159472131 |
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| DOI: | 10.1126/scitranslmed.abd7064 |
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| Publication date in DKUM: | 06.08.2024 |
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| Views: | 426 |
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| Downloads: | 41 |
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| Metadata: |    |
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| Categories: | Misc.
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