Knockdown of Slc11a1 alleviates myocardial ischemia reperfusion-induced injury in mice

Myocardial ischemia-reperfusion (MIR) injury remains the leading cause of adverse outcomes after myocardial infarction, and its prevention remains a major therapeutic challenge.

The GSE160516 and GSE61592 datasets from the Gene Expression Omnibus database were analyzed to screen MIR-related differentially expressed genes. To simulate clinical MIR injury, male C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery for 30 minutes, followed by reperfusion for 24 hours.

In this study, the protein-protein interaction network was generated based on the 34 common upregulated genes, and among them, 11 genes were identified as hub genes, including solute carrier family 11 member 1 (Slc11a1), a gene associated with immune response. Herein, the upregulation of myocardial Slc11a1 was validated in mice with MIR injury. Mice subjected to MIR had improved cardiac function when Slc11a1 was knocked down via myocardial injection of Slc11a1 small interfering RNA (siRNA): the infarcted areas reduced from 38.43±4.13% to 22.18±3.45%; CK-MB levels decreased from 12.01±3.11 to 5.84±1.24. Slc11a1 silencing also reduced infiltration of F4/80 macrophages, deactivated the p65 proinflammatory pathway, and decreased the generation of IL-6 and TNF-α. Myocardial oxidative stress induced by IR challenge was attenuated in mice receiving Slc11a1 siRNA.

Our study demonstrates that the abnormal elevation of Slc11a1 contributes to IR-related myocardial injury.