BACKGROUND: Diabetic cardiomyopathy, characterized by cardiac hypertrophy and contractile dysfunction, eventually leads to heart failure. We have previously shown that alterations of a number of key molecules are involved in producing cardiomyocyte hypertrophy in diabetes. The aim of the present study was to determine whether microRNAs (miRNA) play a role in mediating altered gene expression and structural/functional deficits in the heart in diabetes. METHODS: STZ-induced diabetic mice were haemodynamically investigated after 2 months of diabetes to establish the development of cardiomyopathy. The tissues were then examined for gene expression and microRNA analysis. We further investigated neonatal rat cardiomyocytes to identify the mechanisms of glucose-induced hypertrophy and the potential role of miR133a. RESULTS: Diabetic mice showed myocardial contractile dysfunction and augmented mRNA expression of atrial and brain natriuretic peptides (ANP, BNP), MEF2A and MEF2C, SGK1 and IGF1R compared to age- and sex-matched controls. Cardiac tissues from these mice showed alteration of multiple miRNAs by array analysis including miR133a, which was confirmed by RT-PCR. In vitro exposure of cardiomyocytes to high levels of glucose produced hypertrophic changes and reduced expression of miRNA133a. Finally, transfection of miR133a mimics prevented altered gene expression and hypertrophic changes. CONCLUSION: Data from these studies demonstrate a novel glucose-induced mechanism regulating gene expression and cardiomyocyte hypertrophy in diabetes which is mediated through miR133a. Copyright (c) 2009 John Wiley & Sons, Ltd.
BACKGROUND:Diabetic cardiomyopathy, characterized by cardiac hypertrophy and contractile dysfunction, eventually leads to heart failure. We have previously shown that alterations of a number of key molecules are involved in producing cardiomyocyte hypertrophy in diabetes. The aim of the present study was to determine whether microRNAs (miRNA) play a role in mediating altered gene expression and structural/functional deficits in the heart in diabetes. METHODS:STZ-induced diabeticmice were haemodynamically investigated after 2 months of diabetes to establish the development of cardiomyopathy. The tissues were then examined for gene expression and microRNA analysis. We further investigated neonatal rat cardiomyocytes to identify the mechanisms of glucose-induced hypertrophy and the potential role of miR133a. RESULTS:Diabeticmice showed myocardial contractile dysfunction and augmented mRNA expression of atrial and brain natriuretic peptides (ANP, BNP), MEF2A and MEF2C, SGK1 and IGF1R compared to age- and sex-matched controls. Cardiac tissues from these mice showed alteration of multiple miRNAs by array analysis including miR133a, which was confirmed by RT-PCR. In vitro exposure of cardiomyocytes to high levels of glucose produced hypertrophic changes and reduced expression of miRNA133a. Finally, transfection of miR133a mimics prevented altered gene expression and hypertrophic changes. CONCLUSION: Data from these studies demonstrate a novel glucose-induced mechanism regulating gene expression and cardiomyocyte hypertrophy in diabetes which is mediated through miR133a. Copyright (c) 2009 John Wiley & Sons, Ltd.
Authors: Shyam Sundar Nandi; Hong Zheng; Neeru M Sharma; Hamid R Shahshahan; Kaushik P Patel; Paras K Mishra Journal: Diabetes Date: 2016-07-13 Impact factor: 9.461
Authors: Walter A Baseler; Dharendra Thapa; Rajaganapathi Jagannathan; Erinne R Dabkowski; Tara L Croston; John M Hollander Journal: Am J Physiol Cell Physiol Date: 2012-10-03 Impact factor: 4.249