NMN as a Potential Cardioprotective Agent: Understanding its Mechanisms
Introduction to Cardioprotection
- The SIRT family and their role in metabolic health
- Decline of SIRT activity with age and the investigation into NAD+ precursors
- NMN and NR as orally bioavailable NAD+ precursors undergoing clinical trials
Importance of SIRT1 in Cardioprotection
- Cardiac SIRT1's role in cardioprotective paradigms, including ischemic preconditioning
- NMN's demonstrated cardioprotective effects in a mouse model of ischemia-reperfusion (IR) injury
- Attribution of NMN's activity to SIRT1 stimulation, but limited knowledge of other mechanisms
Investigating NMN-Induced Cardioprotection in Mice
- Use of wild-type and Sirt3-deficient mice in the study
- Langendorff constant flow mode for heart perfusion
- Delivery of NMN, splitomicin (SIRT1 inhibitor), and vehicle during the experiment
- Monitoring cardiac function digitally using a pressure transducer
- Determination of heart infarction using tetrazolium chloride staining
- Metabolomic and glycolytic flux measurements for analysis
- Various tests and assays performed to gather data
Findings of the Study
- NMN-induced cardioprotection not affected by SIRT1 inhibition
- Lysine deacetylation occurred in the mitochondria, suggesting involvement of SIRT3
- Absence of NMN-induced cardioprotection in Sirt3-deficient hearts due to enhanced baseline injury
- NMN stimulation of cardiac glycolysis and cytosolic acidification in primary cardiomyocytes
- Importance of glycolytic stimulation for NMN-induced cardioprotection
- NMN's potential multiple mechanisms of action, including SIRT1, SIRT3, glycolytic stimulation, and acidosis
Implications and Considerations
- Linking NMN-induced glycolysis to enhanced ATP synthesis for cardioprotection
- Understanding the role of acidosis and lysine deacetylation in NMN-induced cardioprotection
- Caution urged in dietary NMN and NR supplementation due to potential negative effects
Supplementary Material and Funding
- Availability of additional material supplementing the main content
- Grants from the US National Institutes of Health supporting the study
- Acknowledgment of technical support and absence of conflicts of interest
Final Remarks
- Status of the provided manuscript as an unedited version accepted for publication
- Mention of upcoming processes before final publication and potential for errors
- Application of legal disclaimers to the manuscript
Title of paper: Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH
Author(s): Nadtochiy SM, Wang YT, Nehrke K, Munger J, Brookes PS.
Year published: 2018
Published in: J Mol Cell Cardiol
Original article can be found here.
