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Dihydromyricetin Prevents Diabetic Cardiomyopathy via miR-34a Suppression by Activating Autophagy
- Source :
- Cardiovascular drugs and therapy. 34(3)
- Publication Year :
- 2020
-
Abstract
- The pro-aging miRNA, miR-34a, is hyperactivated in the cardiac myocardial tissues of patients and mice with diabetes, leading to diabetic cardiomyopathy (DCM). Increasing evidence suggests that dihydromyricetin (DHM) can be used to effectively treat cardiomyopathy. In this study, we investigated whether DHM affects the expression of miR-34a in DCM. The expression of miR-34a in high-glucose-induced cardiomyocytes and in the heart tissue of diabetic mice was determined by microRNA isolation and quantitative reverse transcription-polymerase chain reaction. Lipofectamine 3000 was used to transfect cardiomyocytes with miR-34a inhibitor, miR-34a mimics, and miR-control. These agents were intravenously injected into the tail vein of streptozotocin-induced diabetic mice. Autophagy and apoptosis were assessed in high-glucose-induced cardiomyocytes and cardiac tissue in diabetic mice by western blotting, immunofluorescence, Masson staining, hematoxylin and eosin staining (H&E), and electron microscopy. DHM clearly ameliorated the cardiac dysfunction in the diabetic mice. The expression of miR-34a was up-regulated in high-glucose-induced cardiomyocytes and in the hearts of diabetic mice, thus impairing autophagy. Treatment with DHM decreased the expression of miR-34a and rescued the impairment of autophagy in high-glucose-induced cardiomyocytes and in the heart tissue of diabetic mice, while the miR-34a mimic offset the effect of DHM with respect to the development of DCM by inhibiting autophagy. By decreasing the expression of miR-34a, DHM restores impaired autophagy, and thus ameliorates DCM. Therefore, DHM may potentially be used in the treatment of DCM.
- Subjects :
- 0301 basic medicine
Male
Flavonols
Diabetic Cardiomyopathies
Cardiomyopathy
H&E stain
Autophagy-Related Proteins
Down-Regulation
Apoptosis
030204 cardiovascular system & hematology
Pharmacology
Ventricular Function, Left
Diabetes Mellitus, Experimental
03 medical and health sciences
Mice
0302 clinical medicine
Diabetes mellitus
Diabetic cardiomyopathy
medicine
Autophagy
Animals
Pharmacology (medical)
Myocytes, Cardiac
Rats, Wistar
Cells, Cultured
business.industry
General Medicine
medicine.disease
Blot
MicroRNAs
030104 developmental biology
Lipofectamine
Cardiology and Cardiovascular Medicine
business
Signal Transduction
Subjects
Details
- ISSN :
- 15737241
- Volume :
- 34
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cardiovascular drugs and therapy
- Accession number :
- edsair.doi.dedup.....d35c4eeec1df3a7ffe7d534913655cc8