Department of Medicine, Division of Cardiovascular Medicine
Cardiology | Cardiovascular Diseases | Cell Biology
Despite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associated with post-MI LVRm phenotypes. RNA sequencing of exRNAs was performed on plasma samples from patients with "beneficial" (decrease LVESVI > /=20%, n=11) and "adverse" (increase LVESVI > /=15%, n=11) LVRm. Selected differentially expressed exRNAs were validated by RT-qPCR (n=331) and analyzed for their association with LVRm determined by cardiac MRI. Principal components of exRNAs were associated with LVRm phenotypes post-MI; specifically, LV mass, LV ejection fraction, LV end systolic volume index, and fibrosis. We then investigated the temporal regulation and cellular origin of exRNAs in murine and cell models and found that: 1) plasma and tissue miRNA expression was temporally regulated; 2) the majority of the miRNAs were increased acutely in tissue and at sub-acute or chronic time-points in plasma; 3) miRNA expression was cell-specific; and 4) cardiomyocytes release a subset of the identified miRNAs packaged in exosomes into culture media in response to hypoxia/reoxygenation. In conclusion, we find that plasma exRNAs are temporally regulated and are associated with measures of post-MI LVRm.
inflammation, cardiac magnetic resonance imaging, extracellular RNA, left ventricular remodeling, myocardial infarction, RNA sequencing, microRNA
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Copyright © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
EBioMedicine. 2018 Jun;32:172-181. doi: 10.1016/j.ebiom.2018.05.013. Epub 2018 May 18. Link to article on publisher's site
Danielson KM, Tanriverdi K, Freedman JE, Das S. (2018). Plasma Circulating Extracellular RNAs in Left Ventricular Remodeling Post-Myocardial Infarction. Open Access Articles. https://doi.org/10.1016/j.ebiom.2018.05.013. Retrieved from https://escholarship.umassmed.edu/oapubs/3492
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