Association of Altered Serum MicroRNAs with Perihematomal Edema after Acute Intracerebral Hemorrhage.

Ying Zhu,Zhi-Yi He,Feng Jin,Jia-Lu Wang,Ling Tang,Kandiah Jeyaseelan

doi:10.1371/journal.pone.0133783

Ying Zhu, Zhi-Yi He + Show 4 more

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https://doi.org/10.1371/journal.pone.0133783

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Abstract

Background and PurposePerihematomal edema (PHE) contributes to secondary brain damage and aggravates patient outcomes after intracerebral hemorrhage (ICH). MicroRNAs (miRNAs) are stable in circulation, and their unique expression profiles have fundamental roles in modulating vascular disease. The objective of this study was to test the hypothesis that altered miRNA levels are associated with PHE in ICH patients.MethodsHematoma and PHE volumes of ICH patients were measured on admission and in follow-up computed tomography scans. Whole-genome miRNA profiles of ICH patients and healthy controls were determined using the Exiqon miRCURY LNA Array, and validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Bioinformatics analysis investigated dysregulated miRNA target genes and the signaling pathways involved.ResultsWe identified 55 miRNAs that were differentially expressed in ICH patients compared with normal controls, of which 54 were down-regulated and one was up-regulated. qRT-PCR confirmation showed decreases in miR-126 (0.63-fold), miR-146a (0.64-fold), miR-let-7a (0.50-fold), and miR-26a (0.54-fold) in ICH patients relative to controls. Serum miR-126, but not miR-146a, miR-let-7a or miR-26a, levels were significantly correlated with relative PHE volume on days 3–4 (r = −0.714; P<0.001) in patients with ICH.ConclusionsICH patients appear to have a specific miRNA expression profile. Low expression of miR-126 was positively correlated with the extent of PHE, suggesting it may have a pathogenic role in the development of PHE after ICH.

Highlights

Intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes, and affects over a million people worldwide annually, most of whom either die or are left seriously disabled [1]
We identified 55 miRNAs that were differentially expressed in ICH patients compared with normal controls, of which 54 were down-regulated and one was up-regulated. quantitative reverse transcription-polymerase chain reaction (qRT-polymerase chain reaction (PCR)) confirmation showed decreases in miR-126 (0.63-fold), miR-146a (0.64-fold), miR-let-7a (0.50-fold), and miR-26a (0.54-fold) in ICH patients relative to controls
Serum miR-126, but not miR-146a, miR-let-7a or miR-26a, levels were significantly correlated with relative perihematomal edema (PHE) volume on days 3–4 (r = −0.714; P

Summary

Introduction

Intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes, and affects over a million people worldwide annually, most of whom either die or are left seriously disabled [1]. It is a major public health problem, for which no treatment has yet proven effective. Various factors have been shown to influence the patient outcome in ICH, including age, volume of ICH, hematoma growth, neurologic deficit, presence of intraventricular blood, and infratentorial location [2,3,4] Among these factors, hematoma growth usually occurs in the early phase of ICH, and is strongly associated with poor outcome. The objective of this study was to test the hypothesis that altered miRNA levels are associated with PHE in ICH patients

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