Abstract 16423: Integrated miRNA and mRNA Responses to Acute Human Left Ventricular Ischemia
Background: MicroRNAs (miRNAs) play a significant role in ischemic heart disease. Animal models of left ventricular (LV) ischemia demonstrate a unique miRNA profile, however, these models have limitations in describing human disease. We describe the changes in miRNA that take place following human cardiac ischemia, and integrate this expression profile with whole-genome mRNA changes.
Methods and Results: In nine patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest, high-throughput miRNA and mRNA sequencing was performed on LV tissue obtained immediately after aortic cross clamping (baseline) and before aortic cross clamp removal (post-ischemic). Of 1,237 identified miRNAs, 21 were differentially expressed between baseline and post-ischemic LV samples. Target prediction analysis of these miRNAs was integrated with mRNA expression from the same LV samples to identify anti-correlated miRNA-mRNA pairs. Gene enrichment studies of candidate mRNA targets demonstrated an association with cardiovascular disease, cell death, and metabolism.
Conclusion: This is the first study to establish a miRNA-mRNA expression profile of human left ventricular tissue before and after acute ischemia. Association of differentially expressed miRNAs with predicted target analysis and a mRNA signature was used to generate a list of putative miRNA-mRNA pairs that may regulate acute myocardial injury. Therapeutics that intervene on these miRNA’s and their downstream targets may lead to novel mechanisms of mitigating the damage caused by ischemic insults on the human heart.
Author Disclosures: L.A. Saddic: None. T. Change: None. M.I. Sigurdsson: None. M. Heydarpour: None. B. Raby: None. S.K. Shernan: None. S.F. Aranki: None. S.C. Body: None. J.D. Muehlschlegel: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.