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Updated: Feb 18, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
MicroRNA-145 regulates disabled-2 and Wnt3a expression in cardiomyocytes under hyperglycaemia
Bao-Wei Wang1, Wei-Jen Fang1, Kou-Gi Shyu2
1Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Aims:
MicroRNA-145 (miR-145) could protect cardiomyocyte apoptosis against oxidative stress and repair infarcted myocardium. Angiotensin II (Ang II), a pro-inflammatory cytokine could modulate myocardial remodelling. However, the role of hyperglycaemia on miR-145 expression in cardiomyocyte or diabetes is not known. The effect of Ang II on miR-145 expression under hyperglycaemia in cardiomyocytes remains unknown. We sought to investigate the effect of hyperglycaemia and Ang II on miR-145 expression in cardiomyocytes.
Methods:
Rat cardiomyocytes were cultured under high glucose concentration (25 mmol/L), and streptozotocin-induced diabetic rats were established. TaqMan® MicroRNA real-time quantitative assay was used to quantitate miR-145.
Results:
Sustained high glucose concentration (hyperglycaemia) significantly decreased miR-145 expression in cardiomyocytes. Hyperglycaemia significantly increased Ang II mRNA expression and secretion from rat cardiomyocytes. Ang II suppressed miR-145 expression in cardiomyocytes. Hyperglycaemia increased Dab2 and decreased Wnt3a/ß-catenin expression in cardiomyocytes. Repression of miR-145 expression by Ang II resulted in increased Dab2 and decreased Wnt3a and ß-catenin expression under hyperglycaemia. In contrast, overexpression of miR-145 significantly decreased Dab2 mRNA and protein expression, whereas the mRNA and protein levels for Wnt3a and ß-catenin were significantly reduced in left ventricular myocardium from 5 days to 28 days in diabetic rats. The protein expression patterns of Dab2 and Wnt3a/ß-catenin in left ventricular myocardium of diabetic rats could be reversed upon treatment with valsartan.
Conclusions:
Ang II downregulates miR-145 to regulate Dab2 and Wnt3a/ß-catenin expression in cardiomyocytes under high glucose concentration. Ang II plays a critical role in the regulation of miR-145 in cardiomyocytes under hyperglycaemic conditions.
Insights
Hyperglycemia and Angiotensin II (Ang II) reduce microRNA-145 (miR-145) in heart cells. This impacts Dab2 and Wnt3a/ß-catenin pathways, crucial in diabetic heart conditions.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Diabetes Research
Background:
- MicroRNA-145 (miR-145) shows cardioprotective effects against oxidative stress and myocardial infarction.
- Angiotensin II (Ang II), a pro-inflammatory cytokine, influences myocardial remodeling.
- The impact of hyperglycemia on miR-145 expression in cardiomyocytes and its role in diabetes remain unclear.
Purpose of the Study:
- To investigate the effect of hyperglycemia on miR-145 expression in cardiomyocytes.
- To determine the influence of Ang II on miR-145 expression under hyperglycemic conditions.
- To elucidate the regulatory roles of miR-145, Dab2, and Wnt3a/ß-catenin in diabetic cardiomyopathy.
Main Methods:
- Rat cardiomyocytes were cultured in high glucose (25 mmol/L).
- Streptozotocin-induced diabetic rat models were established.
- miR-145 expression was quantified using TaqMan® MicroRNA real-time quantitative assay.
Main Results:
- Hyperglycemia significantly decreased miR-145 expression and increased Ang II in cardiomyocytes.
- Ang II suppressed miR-145 expression, leading to increased Dab2 and decreased Wnt3a/ß-catenin.
- Overexpression of miR-145 in diabetic rats reduced Dab2 and Wnt3a/ß-catenin levels; valsartan treatment reversed these changes.
Conclusions:
- Angiotensin II downregulates miR-145, affecting Dab2 and Wnt3a/ß-catenin expression in cardiomyocytes under hyperglycemia.
- Ang II plays a key role in regulating miR-145 in cardiomyocytes during hyperglycemic conditions, contributing to diabetic heart complications.
