Abstract 17: MicroRNA-30c Modulates Diabetes-Induced Cardiac Hypertrophy via PI3K/Akt Signaling Pathway
Cardiomyocyte hypertrophy leading to cardiac failure is one of the characteristic alterations in Diabetic Cardiomyopathy. Several regulatory mechanisms mediate altered gene expression in DCM. Alterations in several myocardial miRs have been demonstrated in cardiac hypertrophy but the role of miR-30c in the pathophysiology of diabetes induced cardiac hypertrophy is not known.
Objective: miR-30c may be involved in modulating expression of key genes (Rac1, Cdc42 and Pak1) of PI3K/Akt signalling pathway involved in cardiac hypertrophy in DCM.
Method: DCM was induced in Wistar rats by STZ-high fat diet combination and animals were sacrificed after 12 weeks of diabetes. The expression of miR-30c, Rac1, Cdc42 and Pak1 genes and markers of hypertrophy (ANP and β-MHC) was studied in cardiac tissues (n=6) and control rats (n=6) by qRT-PCR.
Result: We observed 4 fold increased expression of ANP and 2.2 fold of β-MHC genes in DCM group as compared to control group (n=6) (p<0.05). Decreased expression of miR-30c (3.3 fold) was seen in DCM model at 12 weeks compared to control group (n=6) (p<0.05). Expression of three specific targets of miR-30c i.e. Cdc42, Pak1, and Rac1, regulating cardiac hypertrophy, was found to be significantly increased by 1.94 fold, 1.8 fold, and 1.2 fold in cardiac tissues of DCM model respectively and was inversely related to miR-30c expression.
Conclusion: Our results suggest that down regulation of miR-30c in cardiac tissue may play a key role in regulation of diabetes associated cardiac hypertrophy by modulating PI3K/Akt signalling pathway.
- © 2012 by American Heart Association, Inc.