Abstract 19057: Therapeutic Inhibition of Microrna-208a Attenuates Apoptosis, Fibrosis, and Improves Cardiac Function Post Myocardial Infarction
Introduction: MicronRNA-208a is a heart specific microRNA that regulates cardiac stress response. We investigated if Therapeutic inhibition of miR208a using antagomir attenuates apoptosis, fibrosis, and improves cardiac function post Myocardial infarction (MI).
Methods and Results: Adult male C57BL/6 mice had MI induced by ligation of the Left anterior descending coronary artery (LAD) and were randomly assigned to Antagomir, Agomir, or control group. Sham group mice had the same procedure done but without ligation of the LAD. Agomir group received 20nmols of miR-208a agomir for gain of function, and antagomir group received 100nmols of miR-208a antagomir for loss of function, in 0.2mls normal saline as vehicle, while control and sham group received vehicle only. These were sacrificed at day 10 and hearts studied for Apoptosis and Fibrosis. The effect of miR-208a on apoptosis in ischemic cardiomyocytes was studied in cultured neonatal mice myocytes transfected with agomir or antagomir, and compared to control group following simulated ischemia.
To assess the therapeutic benefit of miR-208a silencing at one month post MI, mice received a total of 300nmols of miR208a antagomir, while control and sham group mice received vehicle only.
Results: In vitro, MiR-208a agomir increased bax gene p<0.001 and apoptosis p=0.001, while antagomir decreased bax gene p<0.001 and apoptosis, p=0.029. At 10days post MI, antagomir decreased periinfarct apoptosis p=0.023, and fibrosis p=0.001, while up regulation of miR-208a using agomir increased, periinfarct apoptosis p=0.027 and fibrosis p=0.018. Importantly, therapeutic inhibition of miR-208a significantly improved cardiac contractile function at one month post MI, p=0.009(Figure 1A and B).
Conclusion: MiR-208a antagomir attenuates apoptosis, and fibrosis, and improves cardiac contractile function post MI. Our work lays a foundation for development of miR-208a antagomir as a therapy in MI .
Author Disclosures: H. Tony: None. M. Kai: None. W. Bangwei: None. Z. Qiutang: None.
- © 2014 by American Heart Association, Inc.