Abstract 19454: mmu_circ_008396 a Novel Circular RNA Involved in Myocardial Infarction
Introduction: Recent studies highlighted that circular RNAs (circRNA) can play an important role in cardiac hypertrophy. However, the role of circRNAs post myocardial infarction (MI) has not yet been explored.
Hypothesis: Here, we characterize the expression and function of circRNAs in vitro and in vivo
Methods: Using global circRNA expression profiling, we identified several circRNA transcripts that were differentially regulated post-MI in mice, including mmu_circ_008396 that is significantly down regulated
Results: Interestingly, we found a mmu_circ_008396 circRNA ortholog in humans, which was also significantly down regulated in ischemic cardiomyopathy patients. Corroborating our in vivo findings, in vitro hypoxic insult also significantly down regulated mmu_circ_008396 circRNA expression in cardiomyocytes (neonatal rat ventricular myocytes and h9c2 cells) and mouse endothelial cells. Further, overexpression of mmu_circ_008396 significantly enhanced tube formation and reduced apoptosis of human umbilical vein endothelial cells. For cardiac overexpression of mmu_circ_008396 circRNA, we created AAV9 viral particles and found that in vivo over expression attenuated LV dysfunction post-MI. mmu_circ_008396 circRNA is predicted to bind and potentially sponge 5 miRNAs (mmu-miR-93-3p, mmu-miR-7231-3p, mmu-miR-412-3p, mmu-miR-6998-3p, mmu-miR-298-5p). We show that mmu_circ_008396 binds to its potential target miRNAs and inhibits their activity.
Conclusions: These results indicate that mmu_circ_008396 circRNA might be a novel potential target to prevent cardiac remodeling and also highlight the significance of circRNAs in cardiovascular diseases.
Author Disclosures: V.N. Garikipati: None. S.K. Verma: None. Z. Cheng: None. E. Nickoloff: None. D. Liang: None. M. Khan: None. C. Benedict: None. M. Cimini: None. J. Ibetti: None. L.A. Grisanti: None. S.M. Schumacher: None. E. Gao: None. J.E. Rabinowitz: None. J.E. Wilusz: None. D. Goukassian: None. S.R. Houser: None. W.J. Koch: None. R. Kishore: None.
- © 2016 by American Heart Association, Inc.