Abstract
Diabetic cardiomyopathy (DCM) is a leading cause of death in diabetic patients. Current therapies do not adequately resolve this problem and focus only on the optimal level of blood glucose for patients. Ferroptosis plays an important role in diabetes mellitus and cardiovascular diseases. However, the role of ferroptosis in DCM remains unclear. Differentially expressed ferroptosis-related genes (DE-FRGs) were identified by intersecting GSE26887 dataset and the Ferroptosis Database (FerrDb). The associations between the DE-FRGs and immune cells in DCM, estimated by CIBERSORTx algorithm, were analyzed. Using ow cytometry (FCM) to evaluated the infiltration of immune cells of myocardial tissues. The expression of DE-FRGs, Glutathione peroxidase 4 (GPX4) and Solute carrier family 7 member 11 (SLC7A11) were examined by real-time quantitative PCR and western blotting. 3 DE-FRGs were identified, which are Heat shock protein family B (small) member 1 (HSPB1), Microsomal glutathione S-transferase 1 (MGST1) and solute carrier family 40 member 1 (SLC40A1) respectively, and they were closely linked to immune cells in DCM. In vivo, the levels of CD8 + T cells, B cells and Treg cells were significantly decreased in the DCM group, while the levels of CD4 + T cells, M1 cells, M2 cells and monocytes were increased. Diabetes significantly decreased HSPB1 and MGST1 levels and increased ferroptosis compared to normal group. Furthermore, ferroptosis inhibitor ferrostatin-1 (Fer-1) alleviated high-fat diet (HFD)-induced cadiomyocyte injury and rescued the ferroptosis. This study suggests that ferroptosis related gene HSPB1 and MGST1 are closely related to immune cell infiltration, which may become therapeutic targets for DCM.