Mice underwent 30 minutes of ischemia and received, 5 minutes before reperfusion, 8 mg/kg antagomiR-223 or mismatch-miR treatment, and consecutive injections at day 1 and 2 post-I/R. MiR-223 expression was quantified by in situ hybridization and PCR. Inflammatory cell influx was quantified by immunohistochemistry. By using magnetic resonance imaging (MRI), cardiac dimensions and function were assessed before and 28 days after surgery.
MiR-223 expression significantly increased 1 and 3 days after I/R, corresponding with the inflammatory phase upon cardiac injury. MiR-223 expression mainly increased in myocytes. Inhibition of miR-223 by antagomir treatment significantly reduced total leukocyte (CD45+ cells) and macrophages (Mac-3+ cells) influx at 3 days of reperfusion. End-diastolic volume (EDV) and end-systolic volume (ESV) showed a similar increase in both treatment groups, as well as a comparable decline in ejection fraction (EF) post-I/R.
Although inhibition of miR-223 resulted in less inflammatory influx after reperfusion, this did not lead to less adverse cardiac remodeling. More research on the complex temporal and spatial role of miR-223 during the process of myocardial wound healing is necessary in order to understand the role of miR-223 upon I/R injury and whether it can be used as a novel therapeutic strategy.
Micro-array derived from myocardial tissue showing miRNA expression profiles at different time points after I/R, including miR-223. I/R, ischemia-reperfusion.
