Abstract 201: Protective Effect of Nicotinamide Mononucleotide Administration Against Cardiac Ischemia-Reperfusion Injury
Background: Nicotinamide adenine dinucleotide (NAD) participates in redox reactions as an electron-transferring molecule, thereby serving as a cofactor for metabolism. In the NAD biosynthetic salvage pathway, nicotinamide phosphoribosyltransferase (Nampt) which forms nicotinamide mononucleotide (NMN) is the rate-limiting enzyme and exhibits the protective effect against ischemia/ reperfusion (I/R) injury in the hearts of mice with cardiac-specific overexpression of Nampt. In addition, administration of NMN is reported to reverse the pancreatic beta-cell dysfunction observed in Nampt heterozygous knockout mice.
Methods: To elucidate the protective effect of NMN against cardiac I/R injury, NMN was administered to mice subjected to I/R injury either before ischemia or immediately before reperfusion. Area at risk (AAR) and infarct area (IA) were evaluated 24 hours after reperfusion.
Results: To confirm the distribution of NMN in the heart, NAD and NADH, into which NMN is quickly converted in the heart, were measured. One hour after NMN administration (500mg/ kg body weight, i.p.), the NAD and NADH contents of the NMN group (n=3) were significantly increased, whereas the NAD/NADH ratio was unchanged compared to the vehicle group (n=3) (NAD: NMN=483±42 pmole/mg tissue, vehicle=183±46 pmole/mg tissue, p<0.01; NADH: NMN=262±25 pmole/mg tissue, vehicle=96±17 pmole/mg tissue, p<0.01; NAD/NADH ratio: NMN=1.85±0.09, vehicle=1.82±0.18, n.s.). In the mice administered NMN or vehicle 30 min before ischemia, IA/AAR in the NMN group was smaller than that in the vehicle group (AAR: NMN=26±0.5%, vehicle=27±0.4%, n.s.; IA/AAR: NMN=23±1.8%, vehicle=42±1.5%, p<0.01, n=4). On the other hand, in the mice administered NMN or vehicle immediately before reperfusion, IA/AAR in the NMN group was not different from that in the vehicle group (AAR: NMN=27±0.5%, vehicle=26±1.0%, n.s.; IA/AAR: NMN=37±1.4%, vehicle=34±2.2%, n.s., n=4).
Conclusions: NMN administration significantly increased the NAD content in the heart and exhibited a protective effect against cardiac I/R injury. Increasing NAD content before ischemia, rather than after reperfusion, may minimize I/R injury in clinical settings, such as in acute coronary syndrome before coronary intervention.
- © 2012 by American Heart Association, Inc.