Evidence suggests miRNA-1 may participate in regulating ischemia–reperfusion injury (IRI) by affecting the expression and distribution of connexin 43 (Cx43). To investigate this phenomenon, a recent study by researchers from Tianjin Medical University examined miR-1 expression and its potential role in regulating Cx43 during ischemic postconditioning (IPOST) in a rat model.
In their report, fifty-five Wistar male rats were randomly divided into five groups: N, IR, IPOST, agomir-1, and antagomir-1 group. The hearts were perfused with the Langendorff system. The reperfusion arrhythmia (RA) and myocardial infarct size were observed and recorded. The miRNA-1 expression and the Cx43 expression and distribution were assessed by RT-PCR, immunoblotting, immunohistochemistry and miRNA microarray service.
Experimental protocol: For each isolated rat heart, basal perfusion for 20 min, ischemia for 30 min followed by reperfusion for 2 h. At the beginning of reperfusion, six cycles of 10-s reperfusion/ischemia.
First, it was reported that the RA score in the IR group was higher than that in the control group, whereas there was no difference between the IPOST and antagomir-1 groups. Second, the myocardial infarct size was larger in the agomir-1 than in the IPOST group; there was no difference between the antagomir-1 and the IPOST group. Third, the miRNA-1 expression increased by 78% in the agomir-1 group but decreased by 32% in the antagomir-1 group compared with the IPOST group. Fourth, compared with the Control group, the Cx43 expression in the IR group decreased, the Cx43 expression decreased in the agomir-1 group compared with the IPOST group. Fifth, the distribution of Cx43 was irregular and disorganized in the IR and agomir-1 groups. In the IPOST and antagomir-1 groups, Cx43 was neatly distributed in the intercalated disk area.
These findings suggest that IPOST can inhibit the up-regulation of miRNA-1 induced by ischemia–reperfusion and that the down-regulation of miRNA-1 can prevent the decrease and redistribution of Cx43, which will protect the heart from IRI.