Nicotinamide for the treatment of heart failure with preserved ejection fraction

被引：164

作者：

Abdellatif, Mahmoud ^{[1
]}

Trummer-Herbst, Viktoria ^{[1
]}

Koser, Franziska ^{[2
]}

Durand, Sylvere ^{[3
,4
]}

Adao, Rui ^{[1
,5
]}

Vasques-Novoa, Francisco ^{[5
]}

Freundt, Johanna K. ^{[2
]}

Voglhuber, Julia ^{[1
,6
]}

Pricolo, Maria-Rosaria ^{[7
]}

Kasa, Michael ^{[1
]}

Turk, Clara ^{[8
,9
]}

Aprahamian, Fanny ^{[3
,4
]}

Herrero-Galan, Elias ^{[7
]}

Hofer, Sebastian J. ^{[10
]}

Pendl, Tobias ^{[10
]}

Rech, Lavinia ^{[1
]}

Kargl, Julia ^{[11
]}

Anto-Michel, Nathaly ^{[1
]}

Ljubojevic-Holzer, Senka ^{[1
,6
]}

Schipke, Julia ^{[12
]}

Brandenberger, Christina ^{[12
]}

Auer, Martina ^{[13
,14
]}

Schreiber, Renate ^{[10
]}

Koyani, Chintan N. ^{[1
]}

Heinemann, Akos ^{[11
]}

Zirlik, Andreas ^{[1
]}

Schmidt, Albrecht ^{[1
]}

von Lewinski, Dirk ^{[1
]}

Scherr, Daniel ^{[1
]}

Rainer, Peter P. ^{[1
,6
]}

von Maltzahn, Julia ^{[15
]}

Muhlfeld, Christian ^{[12
]}

Kruger, Marcus ^{[8
,9
]}

Frank, Sasa ^{[6
,13
]}

Madeo, Frank ^{[6
,10
]}

Eisenberg, Tobias ^{[6
,10
]}

Prokesch, Andreas ^{[6
,13
,14
]}

Leite-Moreira, Adelino F. ^{[5
]}

Lourenco, Andre P. ^{[5
]}

Alegre-Cebollada, Jorge ^{[7
]}

Kiechl, Stefan ^{[16
,17
]}

Linke, Wolfgang A. ^{[2
]}

Kroemer, Guido ^{[3
,4
,18
,19
,20
]}

Sedej, Simon ^{[1
,6
,21
]}

机构：

[1] Med Univ Graz, Dept Cardiol, A-8036 Graz, Austria

[2] Univ Munster, Inst Physiol 2, D-48149 Munster, Germany

[3] Inst Gustave Roussy, Metabol & Cell Biol Platforms, F-94805 Villejuif, France

[4] Univ Paris, Sorbonne Univ, Inst Univ France,INSERM U1138, Ctr Rech Cordeliers,Equipe Label Isee Ligue Canc, F-75006 Paris, France

[5] Univ Porto, Fac Med, Cardiovasc Res & Dev Ctr UnIC, Dept Surg & Physiol, P-4200319 Porto, Portugal

[6] BioTechMed Graz, A-8010 Graz, Austria

[7] Ctr Nacl Invest Cardiovasc CNIC, Madrid 28029, Spain

[8] Cologne Excellence Cluster Cellular Stress Respon, Inst Genet, D-50931 Cologne, Germany

[9] Univ Cologne, Ctr Mol Med CMMC, D-50931 Cologne, Germany

[10] Karl Franzens Univ Graz, Inst Mol Biosci, NAWI Graz, A-8010 Graz, Austria

[11] Med Univ Graz, Otto Loewi Res Ctr, Div Pharmacol, A-8010 Graz, Austria

[12] Hannover Med Sch, Inst Funct & Appl Anat, D-30625 Hannover, Germany

[13] Med Univ Graz, Gottfried Schatz Res Ctr Cell Signaling Metab & A, A-8010 Graz, Austria

[14] Med Univ Graz, Div Cell Biol Histol & Embryol, A-8010 Graz, Austria

[15] Leibniz Inst Aging, D-07745 Jena, Germany

[16] Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria

[17] Res Ctr Promoting Vasc Hlth Ageing Community, VASCage, A-6020 Innsbruck, Austria

[18] Hop Europeen Georges Pompidou, AP HP, Pole Biol, F-75015 Paris, France

[19] Chinese Acad Sci, Suzhou Inst Syst Med, Suzhou 215000, Peoples R China

[20] Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, S-17164 Solna, Sweden

[21] Univ Maribor, Fac Med, Maribor 2000, Slovenia

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2021年 / 13卷 / 580期

基金：

奥地利科学基金会;

关键词：

DYSFUNCTION; CONTRIBUTES; MECHANISMS; STRESS; RISK; RATS;

D O I：

10.1126/scitranslmed.abd7064

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页数：15

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