RGD Reference Report - Nicotinamide for the treatment of heart failure with preserved ejection fraction. - Rat Genome Database

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

Authors: 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 
Citation: Abdellatif M, etal., Sci Transl Med. 2021 Feb 10;13(580):eabd7064. doi: 10.1126/scitranslmed.abd7064.
RGD ID: 401965412
Pubmed: PMID:33568522   (View Abstract at PubMed)
PMCID: PMC7611499   (View Article at PubMed Central)
DOI: DOI:10.1126/scitranslmed.abd7064   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diastolic Dysfunction treatmentISOLepr (Rattus norvegicus)401965412DNA:mutations:cds: : (rat)RGD 
Diastolic Dysfunction treatmentIAGP 401965412DNA:mutations:cds: : (rat)RGD 
Diastolic Dysfunction treatmentISOLepr (Rattus norvegicus)401965412 RGD 
Diastolic Dysfunction treatmentIAGP 401965412compared to lean leptin receptor sufficient littermates ZSF1-Leprlean/Crl (RS:0005317), compared to treated obeseRGD 
diastolic heart failure treatmentISOLepr (Rattus norvegicus)401965412; 401965412DNA:mutations:cds: : (rat)RGD 
diastolic heart failure treatmentIAGP 401965412; 401965412 RGD 
obesity treatmentIAGP 401965412; 401965412 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal collagen level treatmentIAGP 401965412; 401965412compared to treatedRGD 
abnormal energy expenditure treatmentIAGP 401965412; 401965412compared to treatedRGD 
abnormal heart left ventricle pressure treatmentIAGP 401965412 RGD 
abnormal heart left ventricle pressure treatmentIAGP 401965412compared to lean leptin receptor sufficient littermates ZSF1-Leprlean/Crl RS:0005317 and compared to treated obeseRGD 
abnormal oxygen consumption treatmentIAGP 401965412 RGD 
abnormal oxygen consumption treatmentIAGP 401965412compared to lean leptin receptor sufficient littermates ZSF1-Leprlean/Crl RS:0005317 and compared to treated obeseRGD 
abnormal white adipose tissue mass treatmentIAGP 401965412; 401965412compared to treatedRGD 
decreased energy expenditure treatmentIAGP 401965412; 401965412 RGD 
heart left ventricle hypertrophy treatmentIAGP 401965412 RGD 
heart left ventricle hypertrophy treatmentIAGP 401965412compared to lean leptin receptor sufficient littermates ZSF1-Leprlean/Crl RS:0005317 and compared to treated obeseRGD 
impaired exercise endurance treatmentIAGP 401965412 RGD 
impaired exercise endurance treatmentIAGP 401965412compared to lean leptin receptor sufficient littermates ZSF1-Leprlean/Crl RS:0005317 and compared to treated obeseRGD 
increased collagen deposition in the muscles treatmentIAGP 401965412; 401965412compared to treatedRGD 
increased systemic arterial systolic blood pressure treatmentIAGP 401965412; 401965412compared to treatedRGD 
increased white adipose tissue mass treatmentIAGP 401965412DNA:mutations:cds: : ratRGD 
increased white adipose tissue mass treatmentIAGP 401965412 RGD 
obese treatmentIAGP 401965412; 401965412 RGD 
pulmonary vascular congestion treatmentIAGP 401965412 RGD 
pulmonary vascular congestion treatmentIAGP 401965412compared to lean leptin receptor sufficient littermates ZSF1-Leprlean/Crl RS:0005317 and compared to treated obeseRGD 
Objects Annotated

Genes (Rattus norvegicus)
Lepr  (leptin receptor)

Genes (Mus musculus)
Lepr  (leptin receptor)

Genes (Homo sapiens)
LEPR  (leptin receptor)

Strains
ZSF1-Leprfa/cp/Crl  (NA)


Additional Information