UMMS Affiliation

Department of Medicine, Division of Cardiovascular Medicine

Publication Date


Document Type



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 (

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

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Full list of authors omitted for brevity. For full list see article.

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Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.



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