Abstract 18945: miR-208a-3p is Downregulated in Cardiac Remodeling and Possibly Controls Gata4 Expression
miR-208a-3p, a cardiac specific microRNA encoded by an intron of the α-myosin heavy chain (α-MHC) gene, is a predicted post-transcriptional repressor of Gata4. Hence, the aim of this work was to correlate the temporal expression profile of miR-208a-3p and Gata4 in cardiac remodeling after myocardial infarction (MI). Wistar rats were submitted to permanent occlusion (PO) of the left anterior descending artery and analyzes were performed in SHAM and MI groups with 2 (n=10 e n=7), 28 (n=8 e n=9) and 90 days post-PO (n=8 e n=9). Cardiac function was examined by echocardiography and Langendorff, while infarct area was obtained from histological analyzes. The relative expression of miR-208a-3p, α-MHC and Gata4 were obtained by RT-qPCR. There were no differences in infarct areas between infarcted animals in all timepoints and functional data were consistent with dilated cardiomyopathy. The relative expression of miR-208a-3p was downregulated both 2 days post-PO (0.12 ± 1.52 p<0.01) and 90 days post-OP (0.18 ± 1.78, p<0.01) in the MI group when compared to SHAM. mRNA levels of α-MHC and Gata4 were also decreased in the MI group at the same times post-PO (α-MHC 2 days: 0.004 ± 6.98, 90 days: 0.05 ± 3.42; Gata4 2 days: 0.25 ±1.54, 90 days: 0.24 ± 3.01). Pearson’s correlation coefficient revealed the existence of a linear correlation between the mRNA levels of Gata4 and α-MHC at 2 days (p=0.0003, R2=0.78) and 90 days post-PO (p<0.0001, R2=0.86). Moreover, the correlation between Gata4 expression and miR-208a-3p was also present at 2 days (p=0.009, R2=0.54) and 90 days post-PO (p=0.04, R2=0.34), as well between α-MHC e miR-208a-3p at 2 days post-PO (p=0.01, R2=0.49). Since miR-208a-3p is coexpressed with α-MHC, which is a direct target of Gata4, we propose that miR-208a-3p decreases Gata4 expression through negative feedback loop. In this context, miR-208a-3p would function as a rheostat, regulating the levels of Gata4.
- © 2013 by American Heart Association, Inc.