Liraglutide alleviates cardiac fibrosis through inhibiting P4hα-1 expression in STZ-induced diabetic cardiomyopathy

: Diabetic cardiomyopathy is an important contributor to morbidity and mortality of diabetic patients by causing heart failure. Interstitial and perivascular fibrosis plays a crucial role in diabetic cardiomyopathy. However, there is a lack of effective specific treatments available for diabetic cardiomyopathy. In the present study, we aim to explore the effects of Liraglutide, a GLP-1 analogue, on diabetic cardiomyopathy in STZ-induced diabetic rats fed with high-fat diet. A total of 60 male Wistar rats were randomly assigned to three groups, i.e. normal group, model group, and Liraglutide group, with 20 rats in each group. Serum levels of TC, TG, LDL-C, NEFA, and hydroxyproline were measured using commercial kits. Cardiac function was evaluated by QRS waves, LVEDd, LVESd, and LVEF. Myocardial fibrosis was measured by immunohistochemistry. Our results demonstrated that chronic administration of Liraglutide decreased the level of blood glucose and significantly alleviated lipid metabolic disturbance compared with the model group. Furthermore, Liraglutide was found to improve the damaged cardiac function. In line with this, we also found that the alleviation of cardiac dysfunction was associated with the decreased fibrosis in diabetic myocardial tissues, which was reflected by the decreased expressions of P4hα-1, COL-1, COL-3, MMP-1, and MMP-9. Our results thus suggest that Liraglutide might have a myocardial protective effect by inhibiting P4hα-1-mediated myocardial fibrosis.