Carbon Monoxide Alleviates Cardiomyocyte Pyroptosis in Diabetic Cardiomyopathy by Downregulating the IL‐33/ST2L Axis

Objectives This study aimed to investigate whether carbon monoxide (CO) can alleviate cardiomyocyte pyroptosis by downregulating the IL‐33/ST2L axis in diabetic cardiomyopathy (DCM). Methods The diabetic mouse model was established and treated with CO‐releasing molecule‐2 (CORM‐2) or invalid CORM‐2 (iCORM‐2). For in vitro studies, cardiomyocytes were treated with high glucose (HG). Results The HG‐treated cardiomyocytes exhibited increased IL‐33, ST2L, and pyroptosis‐related protein expression compared with that in the control group ( p < 0.05). Treatment with recombinant IL‐33 further increased the expression of HG‐induced pyroptosis‐related proteins ( p < 0.05). Compared with control mice, DCM mice showed reduced cardiac function and elevated expression of IL‐33, ST2L, and pyroptosis‐related proteins ( p < 0.01). Intervention with CORM‐2 ameliorated cardiac injury, and decreased the expression of IL‐33, ST2L, and pyroptosis‐related proteins in vivo and in vitro ( p < 0.05). However, iCORM‐2 had no effect both in vivo and in vitro. Conclusions In conclusion, CO may inhibit cardiomyocyte pyroptosis by downregulating the IL‐33/ST2L axis in DCM mice.