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Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
miR-483-3p regulates hyperglycaemia-induced cardiomyocyte apoptosis in transgenic mice
Yu Qiao1, Yanli Zhao2, Yan Liu3
1Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China; Medical Science Institute of Hei Longjiang Province, China.
Abstract:
Diabetic cardiomyopathy represents severe heart complications, and is the leading cause of morbidity and mortality among patients with diabetes. Although a few microRNAs (miRNAs) have been implicated in diabetes-related complications, a functional association between miRNAs and cardiac dysfunction in diabetic cardiomyopathy remains to be demonstrated. Our results show that miR-483-3p is upregulated in streptozotocin-induced diabetic mice, and cultured cardiomyocytes mimicking hyperglycemia. Overexpressing miR-483-3p in transgenic mice with diabetes mellitus (DM) exacerbated cardiomyocyte apoptosis by transcriptionally repressing insulin growth factor 1 (IGF1). Therefore, we have uncovered a novel signaling pathway, involving miR-483-3p-IGF1, that promotes myocardial cell apoptosis under high blood-glucose condition. Further, our study indicates that miR-483-3p could be a potential therapeutic target for managing diabetes-associated heart complications.
Insights
Diabetic cardiomyopathy involves heart complications in diabetes. This study reveals miR-483-3p worsens cardiac apoptosis by targeting insulin growth factor 1 (IGF1), offering a potential therapeutic target.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Molecular Biology
Background:
- Diabetic cardiomyopathy is a major cause of death in diabetic patients.
- The role of microRNAs (miRNAs) in diabetes-related cardiac dysfunction is not fully understood.
- A functional link between specific miRNAs and diabetic cardiomyopathy needs demonstration.
Purpose of the Study:
- To investigate the role of miR-483-3p in diabetic cardiomyopathy.
- To elucidate the signaling pathway involving miR-483-3p in high blood-glucose conditions.
- To identify miR-483-3p as a potential therapeutic target for diabetic heart complications.
Main Methods:
- Upregulation of miR-483-3p was assessed in streptozotocin-induced diabetic mice and cultured cardiomyocytes under hyperglycemia.
- Overexpression of miR-483-3p was studied in transgenic mice with diabetes mellitus (DM).
- The effect of miR-483-3p on insulin growth factor 1 (IGF1) expression was analyzed.
Main Results:
- miR-483-3p was found to be upregulated in diabetic conditions (mice and cell cultures).
- Overexpression of miR-483-3p exacerbated cardiomyocyte apoptosis in diabetic mice.
- miR-483-3p was shown to repress IGF1 transcriptionally, establishing a miR-483-3p-IGF1 signaling pathway.
Conclusions:
- A novel signaling pathway, miR-483-3p-IGF1, promotes myocardial cell apoptosis in hyperglycemia.
- miR-483-3p plays a significant role in the pathogenesis of diabetic cardiomyopathy.
- miR-483-3p represents a promising therapeutic target for managing diabetes-associated heart disease.

