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

EBioMedicine
Kirsty M DanielsonSaumya Das

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 ...Continue Reading

Citations

Jun 13, 2019·Nature Reviews. Cardiology·Dongchao Lu, Thomas Thum
May 28, 2020·Nature Reviews. Molecular Cell Biology·Killian O'BrienXandra O Breakefield
Jun 30, 2019·Frontiers in Genetics·Shengyang JiangBan Liu
Aug 9, 2020·Frontiers in Genetics·Eren M Veziroglu, George I Mias
Aug 20, 2020·Circulation. Genomic and Precision Medicine·Saumya DasUNKNOWN American Heart Association Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular B
May 19, 2020·Circulation Research·Carolin LerchenmüllerAnthony Rosenzweig
Oct 24, 2020·Circulation Research·Jin LiSaumya Das
Oct 24, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Kikuye KoyanoXinshu Xiao
Feb 23, 2020·JACC. Clinical Electrophysiology·Michael G SilvermanSaumya Das
Apr 22, 2019·Current Problems in Cardiology·Yeshun WuChun Yang
Jan 30, 2021·Frontiers in Cell and Developmental Biology·Dongdong ZhengKexiang Liu
May 6, 2021·International Journal of Molecular Sciences·Alina Ioana ScărlătescuMaria Dorobanțu

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Datasets Mentioned

BETA
GSE112690

Methods Mentioned

BETA
electrophoresis
RNAseq
PCA

Clinical Trials Mentioned

NCT00729430

Software Mentioned

Fluidigm
Bioconductor
edgeR
FastX
Ingenuity Pathway analysis
Bowtie2
IPA
sRNABench
IPA Target
Dyrnamix

Related Concepts

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Cardiac remodeling in response to a myocardial infarction is characterized by progressive ventricular dilatation, cardiac hypertrophy, fibrosis, and deterioration of cardiac performance. Discover the latest research on Cardiac Remodeling here.