Abstract 20221: Early Cardioprotective and Chronic Anti-Remodeling Effects of miR-144 in Murine Myocardial Infarction
Introduction: We have previously shown that miR-144 is involved in the acute cardioprotection associated with remote ischemic preconditioning.
Hypothesis: Chronic treatment with miR-144 improves post-MI remodeling.
Methods: Thirty-four C57BL/6 mice were divided into a control PBS-treated group, control scambled miR-Co, and miR-144 treated groups. All mice underwent myocardial infarction (MI) by left anterior descending artery (LAD) ligation. Intravenous MiR 144 at doses of 8 mg/kg, 16mg/kg, or 32mg/kg was given on Day 0, day 1, day 3, and then every three days until day 28 after MI. Cardiac function was evaluated prior to MI and at day 3, day 14 and day 28 using echocardiography and using pressure volume catheter (1.4F; Millar Instruments, Houston, TX, USA) introduced into the left ventricle on day 28. Infarct size was expressed as % of LV. Tissue was analysed by immunohistochemistry.
Results and Conclusions: Ischemia decreased miR-144 levels in mouse myocardium, and was rescued by IV miR-144. Cy3-labelled-miR-144 was predominantly localized to the infarct and border zone, and was taken up by cardiomyocytes and macrophages. Infarct size was significantly reduced in miR 144 treated groups (14.55±1.9% in 8mg/kg, 13.18±0.7% in 16mg/kg, 11.96±2.9% in 32mg/kg groups, all p<0.01 compared with PBS group (25.70±2.6%) and miR-Co (27.52±2.5%) at day 28 post MI, but there was no significant benefit from higher dosage (Figure 1A). Cardiac function was improved in all miR-144 groups (left ventricular fractional shortening, End-systolic Volume (uL), End-diastolic Volume (uL), Ejection Fraction (%), dPdt max (mmHg/sec), dPdt min (mmHg/sec), Tau (msec)), compared with PBS group and miR-Co ( p<0.01). Figure 1B shows the dose-dependent improvement seen in LVFS, for example. Our novel findings provide evidence that miR 144 limits infarct size and provides subsequent protection against pathological cardiac remodeling.
Author Disclosures: J. Li: None. S. Cai: None. Q. He: None. A. Redington: None.
- © 2016 by American Heart Association, Inc.