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Plasma Circulating Extracellular RNAs in Left Ventricular Remodeling Post-Myocardial Infarction.

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.

journal_name

EBioMedicine

journal_title

EBioMedicine

authors

Danielson KM,Shah R,Yeri A,Liu X,Camacho Garcia F,Silverman M,Tanriverdi K,Das A,Xiao C,Jerosch-Herold M,Heydari B,Abbasi S,Van Keuren-Jensen K,Freedman JE,Wang YE,Rosenzweig A,Kwong RY,Das S

doi

10.1016/j.ebiom.2018.05.013

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

172-181

issn

2352-3964

pii

S2352-3964(18)30170-1

journal_volume

32

pub_type

杂志文章,随机对照试验

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