Portal de investigação
Nicotinamide for the treatment of heart failure with preserved ejection fraction
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Abdellatif, M
- Trummer-Herbst, V
- Koser, F
- Durand, S
- Adao, R
- Freundt, JK
- Voglhuber, J
- Pricolo, MR
- Kasa, M
- Türk, C
- Aprahamian, F
- Herrero-Galán, E
- Hofer, SJ
- Pendl, T
- Rech, L
- Kargl, J
- Anto-Michel, N
- Ljubojevic-Holzer, S
- Schipke, J
- Brandenberger, C
- Auer, M
- Schreiber, R
- Koyani, CN
- Heinemann, A
- Zirlik, A
- Schmidt, A
- von Lewinski, D
- Scherr, D
- Rainer, PP
- von Maltzahn, J
- Mühlfeld, C
- Krüger, M
- Frank, S
- Madeo, F
- Eisenberg, T
- Prokesch, A
- Alegre-Cebollada, J
- Kiechl, S
- Linke, WA
- Kroemer, G
- Sedej, S
Unidades de investigação
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.
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Dados da publicação
- ISSN/ISSNe:
- 1946-6234, 1946-6242
- Tipo:
- Article
- Páginas:
- -
- Link para outro recurso:
- www.scopus.com
Science Translational Medicine American Association for the Advancement of Science
Citações Recebidas na Web of Science: 86
Citações Recebidas na Scopus: 123
Documentos
- Não há documentos
Filiações
Keywords
- Animals; Cohort Studies; Heart Failure; Humans; Mice; Mice, Inbred C57BL; Niacinamide; Rats; Rats, Inbred Dahl; Stroke Volume; connectin; nicotinamide; sarcoplasmic reticulum calcium adenosine triphosphatase 2a; sarcoplasmic reticulum calcium transporting adenosine triphosphatase; sirtuin 1; unclassified drug; nicotinamide; adult; aging; animal cell; animal experiment; animal model; animal tissue; antihypertensive activity; Article; bioenergy; cardiac muscle cell; citric acid cycle; comorbidity; controlled study; deacetylation; diastolic dysfunction; female; heart failure with preserved ejection fraction; human; in vitro study; in vivo study; indirect calorimetry; male; mouse; nonhuman; oxidative phosphorylation; rat; RNA sequencing; animal; C57BL mouse; cohort analysis; Dahl rat; heart failure; heart stroke volume
Financiamento
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Citar a publicação
Abdellatif M,Trummer V,Koser F,Durand S,Adao R,Vasques F,Freundt JK,Voglhuber J,Pricolo MR,Kasa M,Türk C,Aprahamian F,Herrero E,Hofer SJ,Pendl T,Rech L,Kargl J,Anto N,Ljubojevic S,Schipke J,Brandenberger C,Auer M,Schreiber R,Koyani CN,Heinemann A,Zirlik A,Schmidt A,von D,Scherr D,Rainer PP,von J,Mühlfeld C,Krüger M,Frank S,Madeo F,Eisenberg T,Prokesch A,Leite AF,Lourenço AP,Alegre J,Kiechl S,Linke WA,Kroemer G,Sedej S. Nicotinamide for the treatment of heart failure with preserved ejection fraction. Sci. Transl. Med. 2021. 13. (580):eabd7064. IF:19,319. (1).
