Identification of Differentially‐Expressed MicroRNAs in the Paraventricular Nucleus (PVN) Following Myocardial Infarction (MI)

Abstract

Alterations in gene regulation in central cardiovascular regulatory regions such as the PVN may play an important role in cardiovascular homeostasis. Given recent evidence suggesting that changes in miRNA expression may be involved in cardiovascular disease, we hypothesized that miRNA expression in the PVN is altered following MI. Microarray analyses for miRNA expression was performed on total RNA samples (n=3) isolated from PVN punches pooled from 5 brains of MI or sham mice using Sangers miRbase V8.0 array specific for mouse. Fifteen miRNAs were differentially regulated (>1.5 fold change between MI and sham mice; 11 up‐regulated, 4 down‐regulated in MI mice). MI‐induced alterations in the expression of mir‐29(a,b,c), mmu‐mir‐9 and ‐9*, and mmu‐mir‐199b were statistically significant (p<0.05; n=3). Up‐regulation of mmu‐mir29c expression was confirmed by real time PCR, and was increased 10‐fold in MI vs. sham mice (p<0.01, n=3). Sequence analysis using miRBase revealed likely interactions of the mmu‐mir‐29 family of micoRNAs with Fos, Agtr2, and MTMR7 genes, some of the highly and specifically expressed genes in neuronal cells. Further studies for confirming the binding of miRNAs to postulated mRNAs are in progress. These studies suggest that differential expression of miRNAs following MI may contribute to changes in gene expression in the PVN involved in MI‐induced heart failure.