Trimetazidine increases plasma MicroRNA-24 and MicroRNA-126 levels and improves dyslipidemia, inflammation and hypotension in diabetic rats

Document Type: Research article

Authors

1 Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

2 Departmentof Physiology, Schoolof Medicine, Ahvaz Jundishapur University of MedicalSciences, Ahvaz,Iran.Persian Gulf Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Atherosclerosis Research Center, Ahvaz Jundishapur University of MedicalSciences, Ahvaz,Iran.

3 Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Persian Gulf Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

4 Departmentof Physiology, Schoolof Medicine, Ahvaz Jundishapur University of MedicalSciences, Ahvaz,Iran.Persian Gulf Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

5 Departmentof Physiology, Schoolof Medicine, Ahvaz Jundishapur University of MedicalSciences, Ahvaz,Iran.Persian Gulf Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,Iran.

Abstract

Trimetazidine (TMZ) improves endothelial dysfunction. However, its beneficial effect on endothelial miRNAs is unexplored in diabetes. The aim of the present study was to evaluate the effects of TMZ on plasma miRNA-24 and miRNA-126, dyslipidemia, inflammation and blood pressure in the diabetic rats. Adult male Sprague-Dawley rats were randomly assigned into four groups (250 ± 20 g, n=8): a control (C), an untreated diabetic (D), a diabetic group administrated with TMZ at 10 mg/kg (T10), and a diabetic group administrated with TMZ at 30 mg/kg (T30) for eight weeks. Diabetes was induced by injection of alloxan (120 mg/kg). The plasma levels of miR-24, miR-126, lipid profile, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), blood glucose, body weight and systolic blood pressure were measured. The diabetic rats showed decreased plasma miR-24, HDL-c (p<0.05), miR-126 (p<0.01), body weight changes percent, body weight, and systolic blood pressure (p<0.001) and increased triglycerides (TG), VLDL-c (p<0.05), TNF-α, total cholesterol (TC) (p<0.01) glucose, MDA and IL-6 (p<0.001). Interestingly, all these changes were significantly improved by TMZ treatment. Our findings propose that TMZ has protective effects on decreased plasma miR-24 and miR-126 levels, inflammation, dyslipidemia and hypotension, and it may participate in endothelial dysfunction and atherosclerosis.

Graphical Abstract

Trimetazidine increases plasma MicroRNA-24 and MicroRNA-126 levels and improves dyslipidemia, inflammation and hypotension in diabetic rats

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