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Early administration of trimetazidine attenuates diabetic cardiomyopathy in rats by alleviating fibrosis, reducing apoptosis and enhancing autophagy.
- Source :
-
Journal of translational medicine [J Transl Med] 2016 Apr 27; Vol. 14 (1), pp. 109. Date of Electronic Publication: 2016 Apr 27. - Publication Year :
- 2016
-
Abstract
- Background: Trimetazidine, as an anti-ischemic and antioxidant agent, has been demonstrated to have many cardioprotective effects. However, whether early administration of trimetazidine has an effect on diabetic cardiomyopathy and the mechanisms underlying the effect have not yet been elucidated.<br />Methods: We established a type 2 DCM rat model by high-fat diet and low-dose streptozotocin. Rats were separated into different groups: control, diabetes, and diabetes + trimetazidine (n = 6, each). Cardiac autophagy, cardiac functions, and cardiomyocyte apoptosis were monitored.<br />Results: Rats with type 2 DCM showed severe insulin resistance, left ventricular dysfunction, increased cardiomyocyte apoptosis, and reduced cardiac autophagy. Collagen volume fraction (CVF) and perivascular collagen area/luminal area (PVCA/LA) ratio were significantly higher in the diabetic group than the control group. We found that trimetazidine treatment ameliorated metabolic disturbance and insulin resistance, reduced cardiomyocyte apoptosis, and restored cardiac autophagy. CVF and PVCA/LA ratio were also lower in the diabetes + trimetazidine group than the diabetic group (CVF, 4.75 ± 0.52 % vs. 11.04 ± 1.67 %, p < 0.05; PVCA/LA, 8.37 ± 0.51 vs. 17.97 ± 2.66, p < 0.05). Furthermore, trimetazidine inhibited phosphorylation of ERK and P38 MAPK to reduce myocardial fibrosis. Inhibited phosphorylation of AMPK was restored and the interaction between Bcl-2 and Beclin1 was enhanced in diabetes + trimetazidine group, resulting in the initiation of autophagy and alleviation of apoptosis.<br />Conclusions: Early administration of trimetazidine could ameliorate diabetic cardiomyopathy by inhibiting myocardial fibrosis and cardiomyocyte apoptosis and enhancing autophagy. Therefore, trimetazidine may be a good choice in the prevention of diabetic cardiomyopathy if applied at the early stage of diabetes.
- Subjects :
- Adenylate Kinase metabolism
Animals
Blood Glucose metabolism
Catheterization
Collagen metabolism
Diabetes Mellitus, Experimental blood
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental metabolism
Diabetic Cardiomyopathies blood
Diabetic Cardiomyopathies metabolism
Diastole
Disease Models, Animal
Fibrosis
Glucose Intolerance blood
Glucose Intolerance complications
Glucose Intolerance pathology
Insulin metabolism
Male
Phosphorylation drug effects
Rats, Sprague-Dawley
Signal Transduction drug effects
Trimetazidine pharmacology
Ventricular Dysfunction, Left physiopathology
Apoptosis drug effects
Autophagy drug effects
Diabetic Cardiomyopathies drug therapy
Diabetic Cardiomyopathies pathology
Trimetazidine administration & dosage
Trimetazidine therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 27121077
- Full Text :
- https://doi.org/10.1186/s12967-016-0849-1