Nicotinamide for the treatment of heart failure with preserved ejection fraction

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Abdellatif, M (Author) Other; Trummer Herbst, V (Author) Other; Koser, F (Author) Other; Durand, S (Author) Other; Adao, R (Author) FMUP; Vasques Novoa, F (Author) FMUP; Freundt, JK (Author) Other; Voglhuber, J (Author) Other; Pricolo, MR (Author) Other; Kasa, M (Author) Other; Turk, C (Author) Other; Aprahamian, F (Author) Other; Herrero Galan, E (Author) Other; Hofer, SJ (Author) Other; Pendl, T (Author) Other; Rech, L (Author) Other; Kargl, J (Author) Other; Anto Michel, N (Author) Other; Ljubojevic Holzer, S (Author) Other; Schipke, J (Author) Other; Brandenberger, C (Author) Other; Auer, M (Author) Other; Schreiber, R (Author) Other; Koyani, CN (Author) Other; Heinemann, A (Author) Other; Zirlik, A (Author) Other; Schmidt, A (Author) Other; von Lewinski, D (Author) Other; Scherr, D (Author) Other; Rainer, PP (Author) Other; von Maltzahn, J (Author) Other; Muhlfeld, C (Author) Other; Kruger, M (Author) Other; Frank, S (Author) Other; Madeo, F (Author) Other; Eisenberg, T (Author) Other; Prokesch, A (Author) Other; Leite-Moreira AF (Author) FMUP; Andre P Lourenco (Author) FMUP; Alegre Cebollada, J (Author) Other; Kiechl, S (Author) Other; Linke, WA (Author) Other; Kroemer, G (Author) Other; Sedej, S (Author) Other

Journal

Title: Science Translational Medicine

Vol. 13

ISSN: 1946-6234

Publisher: American Association for the Advancement of Science

Indexing

ISI Web of Knowledge - 91 Citations

Scopus - 100 Citations

Other information

Authenticus ID: P-00T-JEX

DOI: 10.1126/scitranslmed.abd7064

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15