Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/15164
Título
Nicotinamide for the treatment of heart failure with preserved ejection fraction.
Autor(es)
Abdellatif, Mahmoud | Trummer-Herbst, Viktoria | Koser, Franziska | Durand, Sylvère | Adão, Rui | Vasques-Nóvoa, Francisco | Freundt, Johanna K | Voglhuber, Julia | Pricolo, Maria-Rosaria | Kasa, Michael | Türk, Clara | Aprahamian, Fanny | Herrero-Galán, Elías | Hofer, Sebastian J | Pendl, Tobias | Rech, Lavinia | Kargl, Julia | Anto-Michel, Nathaly | Ljubojevic-Holzer, Senka | Schipke, Julia | Brandenberger, Christina | Auer, Martina | Schreiber, Renate | Koyani, Chintan N | Heinemann, Akos | Zirlik, Andreas | Schmidt, Albrecht | von Lewinski, Dirk | Scherr, Daniel | Rainer, Peter P | von Maltzahn, Julia | Mühlfeld, Christian | Krüger, Marcus | Frank, Saša | Madeo, Frank | Eisenberg, Tobias | Prokesch, Andreas | Leite-Moreira, Adelino F | Lourenço, André P | Alegre-Cebollada, Jorge CNIC | Kiechl, Stefan | Linke, Wolfgang A | Kroemer, Guido | Sedej, Simon
Fecha de publicación
2021
Cita
Sci Transl Med . 2021 Feb 10;13(580):eabd7064
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Heart Failure | Animals | Cohort Studies | Humans | Mice | Mice, Inbred C57BL | Niacinamide | Rats | Rats, Inbred Dahl | Stroke Volume
Versión en línea
DOI
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- Sci Transl Med 2021 Feb 10 ...
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