Bao-Wei Wang1, Wei-Jen Fang1, Kou-Gi Shyu2. 1. Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. 2. Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Abstract
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.
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 diabeticrats 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 diabeticrats. The protein expression patterns of Dab2 and Wnt3a/ß-catenin in left ventricular myocardium of diabeticrats 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.