With the support of National Natural Science Foundation projects (approval numbers: 82325004, 92168114, 82300286, 92168113, 82370458, 82270405), researchers Zhang Yan and Dong Erdan from Peking University, together with the team of Professor Zhang Shuyang and Associate Researcher Hu Xiaomin from Peking Union Medical College Hospital, have made progress in the study of cardiac ischemia/reperfusion injury. The research findings, titled "Extracellular RIPK3 acts as a damage associated molecular pattern to exacerbate cardiac ischemia/reperfusion injury," were published in the journal Circulation on November 26, 2024. Paper link: https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.123.068595 .

　　Ischemia/reperfusion (I/R) injury is an important target for the treatment of ischemic heart disease, and there is currently no effective treatment method to reduce heart I/R injury. Damage associated molecular patterns (DAMPs) are endogenous molecules released by cells after injury, which can exacerbate tissue inflammation and damage. Receptor interacting protein kinase 3 (RIPK3) is an endogenous mediator of cell necrosis and inflammation, which can be detected in peripheral blood and serves as a biomarker for various diseases. However, it is still unknown whether extracellular RIPK3 plays a biological role in cardiac I/R injury.

　　This study found that in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) surgery, plasma RIPK3 concentration was positively correlated with the occurrence of major adverse cardiovascular events (MACE) in the short term (3 months) and long term (5 years), suggesting that RIPK3 is an important biomarker for risk stratification. In cultured cells and in vivo mouse models, recombinant RIPK3 protein, as a novel DAMP, acts on myocardial cells, inflammatory cells, and endothelial cells, causing cell damage, inflammatory response, and functional disorders, thereby participating in the occurrence of myocardial I/R injury. By targeting the extracellular RIPK3 or its downstream receptor of advanced glycation end products (RAGE) - calcium/calmodulin dependent kinase II (CaMKII) signaling pathway, it is expected to provide new strategies for the prevention and treatment of myocardial I/R injury and related complications (Figure).

　　This study revealed a positive correlation between plasma RIPK3 concentration and the risk of major adverse cardiovascular events in AMI patients after PCI treatment, providing a new biomarker for risk stratification in AMI patients and a potential therapeutic target for clinical treatment of cardiac I/R injury.