Nicotinamide Riboside Supplementation Restores Myocardial Nicotinamide Adenine Dinucleotide Levels, Improves Survival, and Promotes Protective Environment Post Myocardial Infarction.

AIMS

Myocardial infarction (MI) is a major cause of death. Nicotinamide adenine dinucleotide (NAD) is a coenzyme in oxidative phosphorylation and substrate of sirtuins and poly-ADP ribose polymerases, enzymes critical for cardiac remodeling post-MI. Decreased NAD is reported in several heart failure models with paradoxically an upregulation of nicotinamide riboside kinase 2, which uses nicotinamide riboside (NR) as substrate in an NAD biosynthetic pathway. We hypothesized that stimulating nicotinamide riboside kinase 2 pathway by NR supplementation exerts cardioprotective effects.

METHODS AND RESULTS

MI was induced by LAD ligation in 2-3-month-old male mice. NR was administered daily (1 µmole/g body weight) over 7 days. RT-PCR showed a 60-fold increase in nicotinamide riboside kinase 2 expression 4 days post-MI with a 60% drop in myocardial NAD and overall survival of 61%. NR restored NAD levels and improved survival to 92%. Assessment of respiration in cardiac fibers revealed mitochondrial dysfunction post-MI, and NR improved complexes II and IV activities and citrate synthase activity, a measure of mitochondrial content. Additionally, NR reduced elevated PARP1 levels and activated a type 2 cytokine milieu in the damaged heart, consistent with reduced early inflammatory and pro-fibrotic response.

CONCLUSION

Our data show that nicotinamide riboside could be useful for MI management.