Extracellular RIPK3 Acts as a Damage-Associated Molecular Pattern to Exaggerate Cardiac Ischemia/Reperfusion Injury
Authors' conclusion
We identified the positive relationship between plasma RIPK3 concentrations and the risk of major adverse cardiovascular events in patients with acute myocardial infarction receiving PCI. As a damage-associated molecular pattern, extracellular RIPK3 plays a causal role in multiple pathological conditions during cardiac I/R injury through RAGE/CaMKII signaling.
Study context
- Population
- Patients with acute MI receiving percutaneous coronary intervention (PCI); neonatal rat ventricular myocytes, macrophages, endothelial cells; mouse I/R models
- Participants
- 103 vs 334
- Comparison
- Discovery vs Validation
- Discoveryn = 103
- Validationn = 334
Methodological detailsdiscovery and validation cohorts, cell culture and mouse I/R models
- Discovery and validation cohorts
- Cell culture and mouse I/R models
Main finding
As reported in the abstract
- Elevated plasma RIPK3 after PCI associated with poorer short- and long-term outcomes in acute MI (discovery cohort, confirmed in validation cohort)
- Recombinant RIPK3 exaggerated myocardial I/R (or hypoxia/reoxygenation) injury in cells and mice; alleviated by RIPK3 antibody
- RIPK3 acted as a damage-associated molecular pattern, bound RAGE and activated CaMKII
- Positive correlation between plasma RIPK3 and CaMKII phosphorylation in human PBMCs
Original publication
Extracellular RIPK3 Acts as a Damage-Associated Molecular Pattern to Exaggerate Cardiac Ischemia/Reperfusion Injury. Circulation. Published 16 October 2024. doi:10.
Summarised from the published abstract; every number is checked against it