Role of micro-RNAs in pathophysiology of diabetic cardiomyopathy.. Rattus norvegicus

Diabetic cardiomyopathy (DCM), occurs independent of Hypertension, Coronary artery disease, or any other known cardiac disease and is characterized by myocardial fibrosis, myocytes loss and hypertrophy. The molecular mechanisms leading to these diseased cardiac phenotype are still being elucidated. A small number of studies have demonstrated that altered expression of several microRNAs are associated with ischemia , mechanical overload, or cardiovascular biology; however, much work is still required to identify individual or group of microRNAs and their role in the pathophysiology of diabetic cardiomyopathy. The aim of present study was to identify the expression of individual or group of microRNAs associated with myocytes hypertrophy and myocardial fibrosis during DCM. MicroRNAs expression profiles were studied in myocardium from High Fat diet and streptozotocin (STZ) induced diabetic (n=4) and non-diabetic (n=2) Wistar rats. All normalized and filtered microRNAs (n=780) processed for differential expression study using unpaired T-test in Gene spring in which unpaired comparison has been performed as test vs. control. After unpaired T-test, total 72 microRNAs were found to be significantly expressed with P-value ≤0.05. Differentially expression analysis was performed and at fold Change cut off ≥ 1.0, all 780 microRNA passed and 39 out of 780 microRNAs were differentially expressed on fold Change cut-off ≥1.5. These results indicate that during the development and progression of DCM, various microRNAs were differentially expressed and may participate in the regulation of various signaling pathways leading to myocytes hypertrophy, apoptosis and cardiac fibrosis. Overall design: After the development and characterization of animal model of DCM, total RNA was isolated from left ventricular tissue of Wistar rats, by RNeasy mini kit Qiagen and microRNA microarray of 6 individual samples (Control sample, n=2 and Test sample, n=4) were performed on Affymetrix microRNA 2.0 plateform. Further, each test samples were compared with mean of 2 control samples for differential microRNA expression and clustering analysis.