Myocardial infarction and revascularization cause cardiac ischemia/reperfusion (I/R) injury featuring cardiomyocyte death and inflammation. The Ca²⁺/calmodulin dependent protein kinase II (CaMKII) family are serine/ threonine protein kinases that are involved in I/R injury. CaMKII exists in four different isoforms, α, β, γ, and δ. In the heart, CaMKII-δ is the predominant isoform，with multiple splicing variants, such as δB, δC and δ9. During I/R, elevated intracellular Ca²⁺ concentrations and reactive oxygen species activate CaMKII. In this review, we summarized the regulation and function of CaMKII in multiple cell types including cardiomyocytes, endothelial cells, and macrophages during I/R. We conclude that CaMKII mediates inflammation in the microenvironment of the myocardium, resulting in cell dysfunction, elevated inflammation, and cell death. However, different CaMKII-δ variants exhibit distinct or even opposite functions. Therefore, reagents/approaches that selectively target specific CaMKII isoforms and variants are needed for evaluating and counteracting the exact role of CaMKII in I/R injury and developing effective treatments against I/R injury.

心肌梗死和血运重建会导致以心肌细胞死亡和炎症为特征的心脏缺血/再灌注（I/R）损伤。Ca ²⁺ /钙调蛋白依赖性蛋白激酶 II (CaMKII) 家族是参与 I/R 损伤的丝氨酸/苏氨酸蛋白激酶。CaMKII 存在四种不同的亚型：α、β、γ 和 δ。在心脏中，CaMKII-δ是主要的亚型，具有多种剪接变体，例如δB、δC和δ9。在 I/R 期间，细胞内 Ca ²⁺浓度升高和活性氧激活 CaMKII。在这篇综述中，我们总结了 CaMKII 在心肌细胞、内皮细胞和巨噬细胞等多种细胞类型中 I/R 过程中的调控和功能。我们得出的结论是，CaMKII 介导心肌微环境中的炎症，导致细胞功能障碍、炎症加剧和细胞死亡。然而，不同的 CaMKII-δ 变体表现出不同甚至相反的功能。因此，需要选择性靶向特定 CaMKII 同工型和变体的试剂/方法来评估和抵消 CaMKII 在 I/R 损伤中的确切作用，并开发针对 I/R 损伤的有效治疗方法。