UMMS Affiliation

Department of Medicine, Division of Cardiovascular Medicine

Publication Date

2018-06-01

Document Type

Article

Disciplines

Cardiology | Cardiovascular Diseases | Cell Biology

Abstract

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.

Keywords

inflammation, cardiac magnetic resonance imaging, extracellular RNA, left ventricular remodeling, myocardial infarction, RNA sequencing, microRNA

Rights and Permissions

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

10.1016/j.ebiom.2018.05.013

Source

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

Journal/Book/Conference Title

EBioMedicine

Comments

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

Related Resources

Link to Article in PubMed

PubMed ID

29779700

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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