Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition
Authors' conclusion
ALDH2 deficiency exacerbates myocardial I/RI by promoting NETosis via the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/LTC4/NOX2 pathway.
Study context
- Population
- Mouse model of myocardial I/RI; STEMI patients after primary PCI
- Participants
- 308 STEMI patients
- Comparison
- Wild-type vs ALDH2 knockout vs Pad4 knockout vs ALDH2/PAD4 double knockout
Main finding
As reported in the abstract
- Enhanced NETosis in human neutrophils carrying the ALDH2 mutation and in ischaemic myocardium of ALDH2 knockout mice vs controls
- PAD4 knockout or NETosis-targeting drugs (GSK484, DNase1) substantially attenuated myocardial damage, particularly in ALDH2 knockout
- ALDH2 deficiency increased damage-associated molecular pattern release and susceptibility to neutrophil extracellular trap (NET)-induced damage
- ALDH2 deficiency induced NOX2-dependent NETosis via ER stress/microsomal glutathione S-transferase 2/LTC4 pathway
- LTC4 receptor antagonist pranlukast ameliorated I/RI by inhibiting NETosis in wild-type and ALDH2 knockout mice
Further findings
Prediction of adverse LV remodelling in STEMI patients · 6 months after primary PCI
- Serum myeloperoxidase-DNA complex and LTC4 levels predicted adverse LV remodelling
Original publication
Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition. Eur Heart J. Published 26 April 2024. doi:10.
Summarised from the published abstract; every number is checked against it