Nicotinamide for the treatment of heart failure with preserved ejection fraction.

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 din...

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Autores: 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, Kiechl, Stefan, Linke, Wolfgang A, Kroemer, Guido, Sedej, Simon
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/15164
Acceso en línea:http://hdl.handle.net/20.500.12105/15164
Access Level:acceso abierto
Palabra clave:Heart Failure
Animals
Cohort Studies
Humans
Mice
Mice, Inbred C57BL
Niacinamide
Rats
Rats, Inbred Dahl
Stroke Volume
Descripción
Sumario: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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