Background -Myocardial metabolic impairment is a major feature in chronic heart failure (HF). As the major coenzyme in fuel oxidation and oxidative phosphorylation and a substrate for enzymes signaling energy stress and oxidative stress response, NAD+ is emerging as a metabolic target in a number of diseases including HF. Little is known on mechanisms regulating homeostasis of NAD+ in the failing heart. Methods -To explore possible alterations of NAD+ homeostasis in the failing heart, we quantified expression of NAD+ biosynthetic enzymes in human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by SRF transcription factor depletion in the heart (SRFHKO) or of cardiac hypertrophy triggered by transverse aorta constriction (TAC). We studied the impact of NAD+ precursor supplementation on cardiac function in both mouse models. Results -We observed a 30% loss in levels of NAD+ in the murine failing heart of both DCM and TAC mice that was accompanied by a decrease in expression of the NAMPT enzyme that recycles the nicotinamide (NAM) precursor whereas the nicotinamide riboside kinase 2 (NMRK2) that phosphorylates the nicotinamide riboside (NR) precursor is increased, to a higher level in the DCM (40 fold) than in TAC (4 fold). This shift was also observed in human failing heart biopsies compared to non-failing controls. We show that the Nmrk2 gene is an AMPK and PPARalpha responsive gene that is activated by energy stress and NAD+ depletion in isolated rat cardiomyocytes. NR efficiently rescues NAD+ synthesis in response to FK866-mediated inhibition of NAMPT and stimulates glycolysis in cardiomyocytes. Accordingly, we show that NR supplementation in food attenuates the development of HF in mice, more robustly in DCM, and partially after TAC, by stabilizing myocardial NAD+ levels in the failing heart. NR treatment also robustly increases the myocardial levels of three metabolites, nicotinic acid adenine dinucleotide, methyl-NAM and N1-Methyl-4-pyridone-5-carboxamide, which can be used as validation biomarkers for the treatment. Conclusions -The data show that nicotinamide riboside, the most energy-efficient among NAD precursors, could be useful for treatment of HF notably in the context of DCM, a disease with few therapeutic options.
Pharmacology, Toxicology and Pharmaceutical Science
7
3%
Sports and Recreations
3
1%
Other
22
10%
Unknown
88
40%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 210. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 September 2026.
All research outputs
#234,253
of 34,433,373 outputs
Outputs from Circulation
#714
of 28,333 outputs
Outputs of similar age
#4,028
of 492,994 outputs
Outputs of similar age from Circulation
#17
of 197 outputs
Altmetric has tracked 34,433,373 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 28,333 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 31.3. This one has done particularly well, scoring higher than 97% of its peers.
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We're also able to compare this research output to 197 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.
