Abstract 11978: Post Infarct Treatment With Microrna145 Protects the Heart Against Myocardial Ischemia Reperfusion Injury Through Acceleration of Myocyte Autophagy
Background: We previously reported that microRNA145 (miR-145) significantly reduced the myocardial infarct size and improved the function of left ventricle.
It has been reported that autophagy is activated in cardiomyocytes in ischemic heart disease. We investigated whether miR-145 would reduce the myocardial infarct size through acceleration of autophagy.
Objective: We aimed to investigate whether administration of miR-145 would affect myocyte autophagy in a rabbit model of myocardial infarction (MI).
Methods: Male Japanese white rabbits underwent 30 min of coronary occlusion followed by 2 and 14 days of reperfusion. Saline or miR-145 (0.035 mg/kg) was intravenous injected immediately after reperfusion. Some of the rabbits treated with miR-145 were administered chloroquine that acts by inhibiting vacuolar H+-ATPase and autophagosome fusion to prevent the final digestion step during autophagy immediately after reperfusion followed by 30 min of coronary ligation. On day 2 and day 14 post-MI, rabbits were sacrificed and the hearts were removed. Heart tissues were sampled and devided into three area; remote area, borderline area and infarct area. The morphological changes were assessed by electron microscopy, and the expressions of LC3B, Akt, phosphorylated (p)-Akt, ERK and p-ERK were assessed by western blot analysis.
Results: The MI size as a percentage of area at risk was significantly smaller in the miR-145 group than that in the control group. Treatment with chloroquine blocked the infarct size-reducing effect of miR-145. These were observed both in 2days and 14days reperfusion groups. Electron microscopic findings showed the autophagic change in cardiomyocytes in both the control and miRNA145 groups on day 2 and day 14 post-MI. Western blot analysis showed that transition from LC3B-I to LC3B-II was significantly stronger in the miR-145 group than in the control group. The expression of p-Akt in the ischemic area was upregulated in the miR-145 group on day 2 post-MI.
However, there was no significant difference in the expression of Akt, ERK and p-ERK between 2 groups on day 2 and day 14 post-MI.
Conclusions: It is suggested that post-infarct treatment with miR-145 attenuated ischemia-reperfusion injury through acceleration of myocyte autophagy.
Author Disclosures: K. Higashi: None. Y. Yamada: None. M. Kumazaki: None. T. Aoyama: None. S. Baba: None. S. Minatoguchi: None. K. Nishigaki: None. G. Takemura: None. Y. Akao: None. S. Minatoguchi: None.
- © 2014 by American Heart Association, Inc.