This topic is lockedThe function(s) of extracellular NAMPT (eNAMPT) is still a somewhat controversial subject. In general terms, injury and inflammation are associated with elevated eNAMPT, which may be either protective (by delivering NAD+ to injured tissues starved for NAD+ by the furious engagement of NAD-consuming enzymes like PARP1, CD38, and SIRT1) or harmful (by increasing inflammation) in different studies. See for instance here, here, and here).
Figure from Nature Reviews Endocrinology 11:535–546 (2015)
In a 2014 paper:
[Overexpressing NAMPT in heart muscle cells] protect the heart against i ischemia/reperfusion (I/R) [which is the main oxidative insult after a heart attack. So does ischaemic preconditioning (IPC) — ie, cyclic pre-exposure to a more moderate level of ischaemia before full-on-I/R, though this effect is unfortunately greatly attenuated or lost altogether with age ]. It remains unknown whether Nampt mediates the protective effect of IPC; whether nicotinamide mononucleotide (NMN, 500 mg/kg [by injection]) ... mimics the effect of IPC, or whether caloric restriction (CR) upregulates Nampt and protects the heart through a Sirt1-dependent mechanism.
IPC upregulated Nampt protein, and the protective effect of IPC against ischemia (30 minutes) and reperfusion (24 hours) was attenuated at both early and late phases in Nampt+/- mice, suggesting that Nampt plays an essential role in mediating the protective effect of IPC. I...
NMN significantly increased the level of NAD+ in the heart at baseline and prevented a decrease in NAD+ during ischemia. NMN protected the heart from I/R injury when it was applied once 30 minutes before ischemia or 4 times just before and during reperfusion ... The protective effect of NMN was accompanied by decreases in acetylation of FoxO1 [a target of SIRT1's deacetylase activity], but it was not obvious in Sirt1 KO mice, suggesting that the effect of NMN is mediated through activation of Sirt1.
Compared to control diet (90% calories), CR (60% calories for 6 weeks) in mice led to a significant reduction in I/R injury, accompanied by upregulation of Nampt. The protective effect of CR against I/R injury was not significant in cardiac-specific Sirt1 KO mice, suggesting that the protective effect of CR is in part mediated through the Nampt-Sirt1 pathway.
PMID: 24905194
A new study, in a different model of heart attack (injection of high-dose potassium to arrest the heart), showed a protective effect of plain-Jane NAM, also after injection:
Nicotinamide Inhibits NAMPT Release and Improves Outcomes in a Murine Model of Cardiac Arrest
Xiangdong Zhu, Jing Li, Chunpei Lee, Huashan Wang, Terry Vander Hoek
Circulation. 2017 Nov 14;136 (Suppl 1):A15531
Hypothesis: Since NAD+ is required for most metabolic processes that generate ATP, we hypothesized that NAM supplementation restores tissue NAD+, blocks NAMPT secretion via inhibition of NADases [ie, NAD-consuming enzymes like PARP1, CD38, and SIRT1], and improves cardiac function and survival in a mouse model of cardiac arrest.
Methods: Adult C57BL6 mice were subjected to an established KCL-induced 8 min cardiac arrest protocol, randomly assigned to receive saline or 100 mg/kg NAM after cardiopulmonary resuscitation (CPR). ...Results: NAM administered IV after CPR significantly improved mouse SCA survival, with 10/10 survival at 4 h as compared to 5/10 in the saline (NS) group (p < 0.01). ... NAM-treated mice displayed improved NAD+ content in hearts ... NAM significantly reduced sorbitol accumulation in heart [which occurs during ischaemia/reperfusion -MR] ... indicating less osmotic injury. NAM also markedly reduced plasma concentrations of NAMPT from 8.9 ± 2.9 ng/ml for saline control to 2.4 ± 0.4 ng/ml.
Conclusion: NAM administered after CPR can rapidly restore cardiac tissue NAD+ and reduce NAMPT release into plasma and facilitate sorbitol clearance in tissues, with improved 4 h survival demonstrated in a mouse model of cardiac arrest.
