PAF Triggered Pyroptotic NETosis Aggravates Myocardial Ischemia/Reperfusion Injury - PubMed
4 hours ago
- #NETosis
- #dapagliflozin
- #myocardial ischemia-reperfusion injury
- PAF (platelet activating factor) secreted by cardiomyocytes during myocardial ischemia-reperfusion (MI/R) injury drives neutrophil extracellular traps (NETs) formation and NETosis.
- Increased expression of PAF synthesis enzyme PLA2G6 leads to excessive PAF production, which requires gasdermin D (GSDMD) for NETosis.
- Inhibiting NETs and PAF synthesis significantly alleviates MI/R injury.
- Dapagliflozin is identified as a potent NETosis inhibitor that protects against MI/R injury in a sodium-glucose co-transporter 2 (SGLT2)-independent manner by targeting neutrophil gelatinase-associated lipocalin-2 (LCN2).
- Increased serum PAF concentration in acute myocardial infarction patients correlates with NETosis and myocardial injury.
- Patients receiving dapagliflozin show attenuated myocardial injury compared to those without it.
- Manipulating the PAF-NETosis signal via dapagliflozin or LCN2 inhibitors may be effective in combating MI/R injury.