Inhibition of HMOX1 alleviates diabetic cardiomyopathy by targeting ferroptosis

Diabetic cardiomyopathy (DCM) is an important complication of chronic diabetes mellitus (DM). However, its pathogenesis and pathologic process have not been fully elucidated. This study was aimed to investigate the role of ferroptosis in the pathogenesis of DCM and clarify the effect of HMOX1 on DCM by targeting ferroptosis. DCM mouse model was constructed by high fat diet (HFD) feeding and streptozotocin (STZ). injection. After 1 week of adaptive feeding, mice were randomly divided into two groups to receive a HFD (60% kcal% fat) or a normal chow for 8 weeks. At the age of 12 weeks, mice fed with HFD were intraperitoneal injected with a low-dose of streptozotocin (STZ, 40 mg/kg, dissolved in 0.1M of citrate acid buffer, # 60256ES80, YEASEN) for 3 consecutive days. Mice fed with normal diet were injected with only citrate acid buffer. Seven days after STZ administration, fasting blood glucose (FBG) were measured and only mice with blood glucose ≥ 11.1mM can be included in the DCM group. After that, mice were continually fed with HFD or normal diet until sacrificed at the age of 25 weeks.