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      The diagnostic value of circulating microRNAs for middle-aged (40–60-year-old) coronary artery disease patients

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          Abstract

          OBJECTIVE:

          Circulating microRNAs have been recognized as promising biomarkers for various diseases. The present study aimed to explore the potential roles of circulating miR-149, miR-424 and miR-765 as non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged (40–60-year-old) patients.

          METHODS:

          Sixty-five stable coronary artery disease patients (49–57 years old), 30 unstable coronary artery disease patients (49–58 years old), and 32 non-coronary artery disease patients (49–-57 years old) who were matched for age, sex, smoking habits, hypertension and diabetes were enrolled in this study. Total RNA was isolated from plasma with TRIzol reagent. Circulating miRNA levels were measured by quantitative real-time polymerase chain reaction.

          RESULTS:

          Circulating miR-149 levels were decreased 4.49-fold in stable coronary artery disease patients (1.18 ± 0.84) and 5.09-fold in unstable coronary artery disease patients (1.04 ± 0.65) compared with non-coronary artery disease patients (5.30 ± 2.57) ( p<0.001). Circulating miR-424 levels were reduced 3.6-fold in stable coronary artery disease patients (1.18 ± 0.60) and 5-fold in unstable coronary artery disease patients (0.86 ± 0.54) compared with non-coronary artery disease patients (4.35 ± 2.20) ( p<0.001). In contrast, circulating miR-765 levels were elevated 3.98-fold in stable coronary artery disease patients (6.09 ± 2.27) and 5.33-fold in unstable coronary artery disease patients (8.17 ± 2.77) compared with non-coronary artery disease patients (1.53 ± 0.99) ( p<0.001). Receiver operating characteristic curve analysis revealed that the respective areas under the curve for circulating miR-149, miR-424 and miR-765 were 0.938, 0.919 and 0.968 in stable CAD patients and 0.951, 0.960 and 0.977 in unstable coronary artery disease patients compared with non-coronary artery disease patients.

          CONCLUSION:

          Our results suggest that circulating miR-149, miR-424 and miR-765 might be novel, non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged patients. However, future prospective trials in large patient cohorts are necessary before reaching a solid conclusion.

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          Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis.

          Eva van Rooij, Lillian Sutherland, Jeffrey Thatcher … (2008)
          Acute myocardial infarction (MI) due to coronary artery occlusion is accompanied by a pathological remodeling response that includes hypertrophic cardiac growth and fibrosis, which impair cardiac contractility. Previously, we showed that cardiac hypertrophy and heart failure are accompanied by characteristic changes in the expression of a collection of specific microRNAs (miRNAs), which act as negative regulators of gene expression. Here, we show that MI in mice and humans also results in the dysregulation of specific miRNAs, which are similar to but distinct from those involved in hypertrophy and heart failure. Among the MI-regulated miRNAs are members of the miR-29 family, which are down-regulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.
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            Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome.

            Christian Widera, Shashi Gupta, Johan M Lorenzen … (2011)
            Circulating microRNAs may have diagnostic potential in acute coronary syndrome (ACS). Previous studies, however, were based on low patient numbers and could not assess the relation of microRNAs to clinical characteristics and their potential prognostic value. We thus assessed the diagnostic and prognostic value of cardiomyocyte-enriched microRNAs in the context of clinical variables and a sensitive myonecrosis biomarker in a larger ACS cohort. MiR-1, miR-133a, miR-133b, miR-208a, miR-208b, and miR-499 concentrations were measured by quantitative reverse transcription PCR in plasma samples obtained on admission from 444 patients with ACS. High-sensitivity troponin T (hsTnT) was measured by immunoassay. Patients were followed for 6 months regarding all-cause mortality. In a multiple linear regression analysis that included clinical variables and hsTnT, miR-1, miR-133a, miR-133b, and miR-208b were independently associated with hsTnT levels (all P<0.001). Patients with myocardial infarction presented with higher levels of miR-1, miR-133a, and miR-208b compared with patients with unstable angina. However, all six investigated microRNAs showed a large overlap between patients with unstable angina or myocardial infarction. MiR-133a and miR-208b levels were significantly associated with the risk of death in univariate and age- and gender-adjusted analyses. Both microRNAs lost their independent association with outcome upon further adjustment for hsTnT. The present study tempers speculations about the potential usefulness of cardiomyocyte-enriched microRNAs as diagnostic or prognostic markers in ACS. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Human traumatic brain injury alters plasma microRNA levels.

              John Redell, Anthony Moore, Norman Ward … (2010)
              Circulating microRNAs (miRNAs) present in the serum/plasma are characteristically altered in many pathological conditions, and have been employed as diagnostic markers for specific diseases. We examined if plasma miRNA levels are altered in patients with traumatic brain injury (TBI) relative to matched healthy volunteers, and explored their potential for use as diagnostic TBI biomarkers. The plasma miRNA profiles from severe TBI patients (Glasgow Coma Scale [GCS] score ≤8) and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. Of the 108 miRNAs identified in healthy volunteer plasma, 52 were altered after severe TBI, including 33 with decreased and 19 with increased relative abundance. An additional 8 miRNAs were detected only in the TBI plasma. We used quantitative RT-PCR to determine if plasma miRNAs could identify TBI patients within the first 24 h post-injury. Receiver operating characteristic curve analysis indicated that miR-16, miR-92a, and miR-765 were good markers of severe TBI (0.89, 0.82, and 0.86 AUC values, respectively). Multiple logistic regression analysis revealed that combining these miRNAs markedly increased diagnostic accuracy (100% specificity and 100% sensitivity), compared to either healthy volunteers or orthopedic injury patients. In mild TBI patients (GCS score > 12), miR-765 levels were unchanged, while the plasma levels of miR-92a and miR-16 were significantly increased within the first 24 h of injury compared to healthy volunteers, and had AUC values of 0.78 and 0.82, respectively. Our results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clinics (Sao Paulo)
                Journal ID (iso-abbrev): Clinics (Sao Paulo)
                Title: Clinics
                Publisher: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
                ISSN (Print): 1807-5932
                ISSN (Electronic): 1980-5322
                Publication date (Print): April 2015
                Volume: 70
                Issue: 4
                Pages: 257-263
                Affiliations
                [I ]Central South University, Xiangya Hospital, Department of Cardiology, Changsha, China
                [II ]Harvard Medical School, Brigham and Women's Hospital, Center for Vascular Biology and Inflammation, Department of Medicine, Cardiovascular Division, Boston, U.S.A.
                [III ]Central South University, Xiangya 3rd Hospital, Department of Gynecology and Obstetrics, Changsha, China
                [IV ]Central South University, School of Pharmaceutical Sciences, Department of Pharmacology, Changsha, China
                Author notes

                Sayed AS and Xia K designed the research, performed the experiments and wrote the manuscript. Deng X, Deng H, Yangda F, Li F, Haoyang Z, Li T, and Salma U collected patient samples and assembled the data. Yang T and Peng J supervised the data analysis and revised the manuscript. The work presented in this paper was performed in collaboration with all the authors.

                Article
                Publisher ID: cln_70p257
                DOI: 10.6061/clinics/2015(04)07
                PMC ID: 4418278
                SO-VID: a826596c-f86a-4608-b97b-6392484ae8b0
                Copyright © Copyright © 2015 Hospital das Clínicas da FMUSP
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 6 August 2014
                Date revision received : 8 October 2014
                Date accepted : 27 January 2015
                Page count
                Pages: 7
                Categories
                Subject: Clinical Science

                ScienceOpen disciplines: Medicine
                Keywords: circulating micrornas,coronary artery disease,unstable angina,biomarkers,non-coronary artery disease
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: circulating micrornas, coronary artery disease, unstable angina, biomarkers, non-coronary artery disease

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