Abdellatif, Mahmoud ORCID: 0000-0002-5042-9054, Trummer-Herbst, Viktoria, Koser, Franziska, Durand, Sylvere, Adao, Rui, Vasques-Novoa, Francisco ORCID: 0000-0001-9701-8538, Freundt, Johanna K., Voglhuber, Julia ORCID: 0000-0003-0102-7902, Pricolo, Maria-Rosaria, Kasa, Michael ORCID: 0000-0002-0273-3019, Turk, Clara, Aprahamian, Fanny, Herrero-Galan, Elias, Hofer, Sebastian J., Pendl, Tobias, Rech, Lavinia ORCID: 0000-0002-0787-446X, Kargl, Julia ORCID: 0000-0002-0870-0816, Anto-Michel, Nathaly, Ljubojevic-Holzer, Senka ORCID: 0000-0001-6994-9976, Schipke, Julia, Brandenberger, Christina, Auer, Martina, Schreiber, Renate, Koyani, Chintan N., Heinemann, Akos, Zirlik, Andreas, Schmidt, Albrecht ORCID: 0000-0003-4783-4603, von Lewinski, Dirk, Scherr, Daniel, Rainer, Peter P., von Maltzahn, Julia ORCID: 0000-0001-7674-1487, Muhlfeld, Christian, Kruger, Marcus, Frank, Sasa, Madeo, Frank ORCID: 0000-0002-5070-1329, Eisenberg, Tobias ORCID: 0000-0003-3559-1130, Prokesch, Andreas, Leite-Moreira, Adelino F. ORCID: 0000-0001-7808-3596, Lourenco, Andre P., Alegre-Cebollada, Jorge ORCID: 0000-0003-0542-0170, Kiechl, Stefan, Linke, Wolfgang A., Kroemer, Guido and Sedej, Simon ORCID: 0000-0002-4419-6821 (2021). Nicotinamide for the treatment of heart failure with preserved ejection fraction. Sci. Transl. Med., 13 (580). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1946-6242

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Abdellatif, MahmoudUNSPECIFIEDorcid.org/0000-0002-5042-9054UNSPECIFIED
Trummer-Herbst, ViktoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koser, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Durand, SylvereUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adao, RuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vasques-Novoa, FranciscoUNSPECIFIEDorcid.org/0000-0001-9701-8538UNSPECIFIED
Freundt, Johanna K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voglhuber, JuliaUNSPECIFIEDorcid.org/0000-0003-0102-7902UNSPECIFIED
Pricolo, Maria-RosariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kasa, MichaelUNSPECIFIEDorcid.org/0000-0002-0273-3019UNSPECIFIED
Turk, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aprahamian, FannyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrero-Galan, EliasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofer, Sebastian J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pendl, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rech, LaviniaUNSPECIFIEDorcid.org/0000-0002-0787-446XUNSPECIFIED
Kargl, JuliaUNSPECIFIEDorcid.org/0000-0002-0870-0816UNSPECIFIED
Anto-Michel, NathalyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ljubojevic-Holzer, SenkaUNSPECIFIEDorcid.org/0000-0001-6994-9976UNSPECIFIED
Schipke, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brandenberger, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Auer, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreiber, RenateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koyani, Chintan N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinemann, AkosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zirlik, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, AlbrechtUNSPECIFIEDorcid.org/0000-0003-4783-4603UNSPECIFIED
von Lewinski, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scherr, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rainer, Peter P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Maltzahn, JuliaUNSPECIFIEDorcid.org/0000-0001-7674-1487UNSPECIFIED
Muhlfeld, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kruger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frank, SasaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madeo, FrankUNSPECIFIEDorcid.org/0000-0002-5070-1329UNSPECIFIED
Eisenberg, TobiasUNSPECIFIEDorcid.org/0000-0003-3559-1130UNSPECIFIED
Prokesch, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leite-Moreira, Adelino F.UNSPECIFIEDorcid.org/0000-0001-7808-3596UNSPECIFIED
Lourenco, Andre P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alegre-Cebollada, JorgeUNSPECIFIEDorcid.org/0000-0003-0542-0170UNSPECIFIED
Kiechl, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linke, Wolfgang A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroemer, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sedej, SimonUNSPECIFIEDorcid.org/0000-0002-4419-6821UNSPECIFIED
URN: urn:nbn:de:hbz:38-605261
DOI: 10.1126/scitranslmed.abd7064
Journal or Publication Title: Sci. Transl. Med.
Volume: 13
Number: 580
Date: 2021
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1946-6242
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DYSFUNCTION; CONTRIBUTES; MECHANISMS; STRESS; RISK; RATSMultiple languages
Cell Biology; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60526

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