Trimetazidine inhibits cardiac fibrosis by reducing reactive oxygen species and downregulating connective tissue growth factor in streptozotocin-induced diabetic rats
Abstract
Diabetes may affect myocardial fibrosis through oxidative stress. Trimetazidine (TMZ) is an anti-anginal agent. The present study aimed to determine the modulatory effect of TMZ on reactive oxygen species (ROS) and connective tissue growth factor (CTGF) expression and to evaluate the potential of TMZ to improve diastolic function in streptozotocin (STZ)-induced diabetic rats. After treating STZ-induced diabetic rats with TMZ for 16 weeks, a decrease in malondialdehyde levels, cardiac collagen volume fraction, left ventricular (LV) end-diastolic pressure and protein expression of collagen-I (Col I), Col III and CTGF compared with those in diabetic control rats was observed. In vitro, TMZ inhibited Col I, Col III and CTGF protein expression in cardiac fibroblasts treated with high glucose and decreased intracellular ROS generation and hydroxyproline content in the cell culture medium of cardiac fibroblasts. TMZ markedly improved cardiac fibrosis and diastolic function in diabetic rats. This effect was associated with a reduction in ROS production and CTGF expression in cardiac fibroblasts. The present study suggests that TMZ may be beneficial for protecting the hearts of diabetic patients.
References
Trimetazidine inhibits neutrophil accumulation after myocardial ischaemia and reperfusion in rabbits
Induction of connective tissue growth factor in retinal pigment epithelium cells by oxidative stress
Notch signaling may negatively regulate neonatal rat cardiac fibroblast-myofibroblast transformation
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