Plasma MicroRNAs as Potential Noninvasive Biomarkers for In-Stent Restenosis

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Abstract

Objective

To investigate whether microRNAs (miRs) can serve as novel biomarkers for in-stent restenosis (ISR).

Methods

This retrospective, observational single-centre study was conducted at the cardiovascular department of a tertiary hospital centre in the north of China. Follow-up coronary angiography at 6 to 12 months was performed in 181 consecutive patients implanted with drug-eluting stents. Fifty-two healthy volunteers served as the control group. The plasma miRs levels were analyzed by quantitative real-time PCR. Receiver-operating characteristic curve (ROC) analysis was performed to investigate the characters of these miRs as potential biomarkers of ISR.

Results

MiR-21 levels in ISR patients were significantly higher than those in non-ISR patients and healthy controls ( P<0.05), while miR-100 ( P<0.05), miR-143 ( P<0.001) and miR-145 ( P<0.0001) levels were significantly decreased in ISR patients. Further analysis showed that miR-21 levels were remarkably increased ( P = 0.045), while miR-100 ( P = 0.041), miR-143 ( P = 0.029) and miR-145 ( P<0.01) levels were dramatically decreased in patients with diffuse ISR compared to those with focal ISR. ROC analysis demonstrated that the area under curve of miR-145, miR-143, miR-100 and miR-21 were 0.880 (95% confidence interval; CI = 0.791–0.987, P<0.001), 0.818 (95% confidence interval; CI = 0.755–0.963, P<0.001), 0.608 (95% confidence interval; CI = 0.372–0.757, P<0.05) and 0.568 (95% confidence interval; CI = 0.372–0.757, P<0.05), with specificity of 83.1%, 80.1%, 68.9% and 68.6%, and sensitivity of 88.7%, 82.1%, 60.2% and 50.1%, respectively.

Conclusions

Circulating miR-143 and miR-145 levels are associated with the occurrence of ISR and can serve as novel noninvasive biomarkers for ISR.

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Most cited references 30

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miRecords: an integrated resource for microRNA–target interactions

Feifei Xiao, Zhixiang Zuo, Guoshuai Cai … (2009)

MicroRNAs (miRNAs) are an important class of small noncoding RNAs capable of regulating other genes’ expression. Much progress has been made in computational target prediction of miRNAs in recent years. More than 10 miRNA target prediction programs have been established, yet, the prediction of animal miRNA targets remains a challenging task. We have developed miRecords, an integrated resource for animal miRNA–target interactions. The Validated Targets component of this resource hosts a large, high-quality manually curated database of experimentally validated miRNA–target interactions with systematic documentation of experimental support for each interaction. The current release of this database includes 1135 records of validated miRNA–target interactions between 301 miRNAs and 902 target genes in seven animal species. The Predicted Targets component of miRecords stores predicted miRNA targets produced by 11 established miRNA target prediction programs. miRecords is expected to serve as a useful resource not only for experimental miRNA researchers, but also for informatics scientists developing the next-generation miRNA target prediction programs. The miRecords is available at http://miRecords.umn.edu/miRecords.

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Mechanisms of gene silencing by double-stranded RNA.

Gunter Meister, Thomas Tuschl (2004)

Double-stranded RNA (dsRNA) is an important regulator of gene expression in many eukaryotes. It triggers different types of gene silencing that are collectively referred to as RNA silencing or RNA interference. A key step in known silencing pathways is the processing of dsRNAs into short RNA duplexes of characteristic size and structure. These short dsRNAs guide RNA silencing by specific and distinct mechanisms. Many components of the RNA silencing machinery still need to be identified and characterized, but a more complete understanding of the process is imminent.

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miR-145 and miR-143 Regulate Smooth Muscle Cell Fate Decisions

Kimberly Cordes, Neil T. Sheehy, Mark White … (2009)

SUMMARY microRNAs are regulators of myriad cellular events, but evidence for a single microRNA that can efficiently differentiate multipotent cells into a specific lineage or regulate direct reprogramming of cells into an alternate cell fate has been elusive. Here, we show that miR-145 and miR-143 are co-transcribed in multipotent cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem cell–derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2.5, and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells. miR-145 was necessary for myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce differentiation of multipotent neural crest stem cells into vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a network of transcription factors, including Klf4, myocardin, and Elk-1 to promote differentiation and repress proliferation of smooth muscle cells. These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells.

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Author and article information

Contributors

Andre van Wijnen: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 26 November 2014

Volume: 9

Issue: 11

Electronic Location Identifier: e112043

Affiliations

[1 ]Cardiovascular Department, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, P.R. China

[2 ]Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang Province, P.R. China

[3 ]Cardiovascular Department, the Hospital of Heilongjiang Province, Harbin, Heilongjiang Province, P.R. China

[4 ]Life Science and Technology College of Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R. China

[5 ]Wyeth Research, Cambridge, MA, United States of America

University of Massachusetts Medical, United States of America

Author notes

* E-mail: ly99ly@ 123456vip.163.com

Competing Interests: In this study, only one author (X. Tan) is employed by a commercial company (Wyeth Research). He is responsible for fundamental research in Wyeth Research. He is only on staff and his work is not related to the consultancy, patents, products in development, or marketed products. In this study, he worked hard to correct the grammatical errors, so the authors put his name in the manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Analyzed the data: MH YG JS HZ. Wrote the paper: MH YG JS ZP YL. Provided the conception and design, overall direction and supervision of the project: YL. Designed the statistical analysis strategies: X. Tu WL BL. Collected and managed clinical samples from the patients: DS JX LS CX NY HX CY. Collected and managed clinical samples from normal subjects: LS HX. Carried out Real-Time RT-PCR: MH YG JS HZ XD. Coordinated the projects: MH YG JS ZP X. Tu WL. Corrected the grammatical errors of the manuscript: X. Tan JL.

Article

Publisher ID: PONE-D-14-06108

DOI: 10.1371/journal.pone.0112043

PMC ID: 4245195

PubMed ID: 25427155

SO-VID: 58738004-7e28-4b72-baa8-bbc2a9d8a664

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 27 March 2014

Date accepted : 11 October 2014

Page count

Pages: 22

Funding

This work was supported by a grant of National Basic Research Program of China (973 program, 2014CB542401 to YL), Natural Science Foundation of China (No. 30971251, 81070160, 81470462, 81100121, 81100071), the Heilongjiang Province Outstanding Youth Foundation (No. JC201208), the Collegiate Changjiang Scholar Reserve Support Plan of Heilongjiang Province (No. 2013CJHB001), the grants for study abroad from the Heilongjiang Provincial Science and Technology agency (No. LC08C36). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Data Availability The authors confirm that all data underlying the findings are fully available without restriction. The raw data of the study is available at the publicly available database ( www.medresman.org, ChiCTR-OCH-14004263).

Plasma MicroRNAs as Potential Noninvasive Biomarkers for In-Stent Restenosis

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Abstract

Objective

Methods

Results

Conclusions

Related collections

PLOS Climate

Most cited references 30

miRecords: an integrated resource for microRNA–target interactions

Mechanisms of gene silencing by double-stranded RNA.

miR-145 and miR-143 Regulate Smooth Muscle Cell Fate Decisions

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Contributors

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