Abstract 15227: Microrna-21 Contributes to Diabetic Cardiomyopathy Associated Cardiac Fibrosis
Background: Myocardial fibrosis is most common pathological feature of Diabetic Cardiomyopathy (DCM) and is associated with differential expression of fibrogenic genes in diabetic heart. Several microRNAs (miRs) have been found to modulate gene expression in different experimental settings of cardiac fibrosis. Current knowledge on role of microRNAs in DCM associated myocardial fibrosis is limited. In the present study, we examined role of fibroblast specific miR-21 in DCM associated cardiac fibrosis.
Methods and Results: Expression of miR-21 was studied in cardiac autopsy tissues from DCM patients (n=6) by qRT-PCR. Myocardial expression of miR-21 showed 11 fold increase in the DCM group as compared to control tissue (n=6). Further, myocardial expression of miR-21 and profibrotic genes (CTGF, FGF-b, TGF-b and FN) was assessed in a rodent model of DCM (streptozotocin and high fat diet induced)in-vivo and in primary rat cardiac fibroblasts in-vitro. We observed 15 fold increased expression of miR-21 in DCM group (n=6) as compared to control group (n=6). Myocardial mRNA levels of profibrotic genes were also significantly increased in DCM group (p<0.05) and showed a positive correlation with miR-21 expression. Cardiac fibroblasts incubated with high glucose (25mM) for 72 hours also showed 10 fold increased miR-21 expression, along with increased expression of profibrotic genes as compared to cells incubated with normal glucose concentration (5mM) (p<0.05). We also found significant increase in myocardial mRNA levels of PTEN (Phosphatase and tensin homolog deleted on chromosome 10), which is a potential target of miR-21, in DCM group (5 fold) and in fibroblasts (4 fold) exposed to high glucose (p<0.05) as compared to their respective control groups.
Conclusion: Our data suggests that increased expression of fibroblast specific miR-21 may mediate cardiac fibrosis by modulating PTEN in DCM.
- © 2011 by American Heart Association, Inc.