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      Altered microRNA dynamics in acute coronary syndrome

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          Abstract

          Introduction

          In the course of acute myocardial infarction (AMI) cardiomyocyte injury, activation and destruction of endothelial cells together with inflammation lead to miRNA expression alterations.

          Aim

          To assess levels of circulating cardiac-specific (miR-1) and endothelial-specific (miR-126) miRNAs in the acute phase of AMI and after a follow-up period.

          Material and methods

          Seventeen AMI patients (mean age: 64.24 ±13.83 years, mean left ventricle ejection fraction (LVEF): 42.6 ±9.65%), treated with primary percutaneous coronary intervention within the first 12 h, had plasma miRNAs isolated (quantitative real-time PCR, Exiqon) on admission and after 19.2 ±5.9 weeks. Measurements were also performed in a control group of healthy volunteers matched for age and sex.

          Results

          Concentrations of both miRNAs were significantly higher in AMI patients as compared to healthy controls: miR-1: 5.93 (3.15–14.92) vs. 1.46 (0.06–2.96), p = 0.04; miR-126: 4.5 (3.11–7.64) vs. 0.54 (0.36–0.99), p = 0.00003, respectively. Levels of both miRNAs significantly decreased after the follow-up period: miR-1: 5.93 (3.15–14.92) vs. 1.34 (0.04–2.34), p = 0.002; miR-126: 4.5 (3.11–7.64) vs. 1.18 (0.49–1.68), p = 0.0005). Moreover, miR-1 correlated positively with maximal troponin I concentration ( r = 0.59, p = 0.02) and negatively with LVEF ( r = –0.76, p = 0.0004).

          Conclusions

          In our study, miR-1 emerged as a marker of cardiomyocyte injury and loss of myocardial contractility, whereas dynamics of miR-126 concentration may reflect endothelial activation and damage in the most extreme stage of atherosclerosis, followed by angiogenesis in ischemic myocardium. However, to fully elucidate the role of miR-1 and miR-126 as biomarkers of AMI and future therapeutic targets, further research is required.

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          Most cited references39

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          Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases.

          Dysregulated expression of microRNAs (miRNAs) in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.
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            Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis.

            Gradients of signalling and transcription factors govern many aspects of embryogenesis, highlighting the need for spatiotemporal control of regulatory protein levels. MicroRNAs are phylogenetically conserved small RNAs that regulate the translation of target messenger RNAs, providing a mechanism for protein dose regulation. Here we show that microRNA-1-1 (miR-1-1) and miR-1-2 are specifically expressed in cardiac and skeletal muscle precursor cells. We found that the miR-1 genes are direct transcriptional targets of muscle differentiation regulators including serum response factor, MyoD and Mef2. Correspondingly, excess miR-1 in the developing heart leads to a decreased pool of proliferating ventricular cardiomyocytes. Using a new algorithm for microRNA target identification that incorporates features of RNA structure and target accessibility, we show that Hand2, a transcription factor that promotes ventricular cardiomyocyte expansion, is a target of miR-1. This work suggests that miR-1 genes titrate the effects of critical cardiac regulatory proteins to control the balance between differentiation and proliferation during cardiogenesis.
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              Identification of novel genes coding for small expressed RNAs.

              In Caenorhabditis elegans, lin-4 and let-7 encode 22- and 21-nucleotide (nt) RNAs, respectively, which function as key regulators of developmental timing. Because the appearance of these short RNAs is regulated during development, they are also referred to as small temporal RNAs (stRNAs). We show that many 21- and 22-nt expressed RNAs, termed microRNAs, exist in invertebrates and vertebrates and that some of these novel RNAs, similar to let-7 stRNA, are highly conserved. This suggests that sequence-specific, posttranscriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated.
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                Author and article information

                Journal
                Postepy Kardiol Interwencyjnej
                Postepy Kardiol Interwencyjnej
                PWKI
                Postępy w Kardiologii Interwencyjnej = Advances in Interventional Cardiology
                Termedia Publishing House
                1734-9338
                1897-4295
                02 October 2020
                September 2020
                : 16
                : 3
                : 287-293
                Affiliations
                [1 ]Department of Cardiology, Medical University of Bialystok, Bialystok, Poland
                [2 ]Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland
                [3 ]Department of Population Medicine and Civilization Diseases Prevention, Medical University of Bialystok, Bialystok, Poland
                [4 ]Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
                Author notes
                Corresponding author:Ewelina Kazimierczyk MD, PhD, Department of Cardiology, Medical University of Bialystok, Bialystok, Poland, e-mail: e-kazimierczyk@ 123456wp.pl
                Article
                41849
                10.5114/aic.2020.99263
                7863810
                33597993
                bfa86762-fc70-4195-85d2-05ce1e279ebc
                Copyright © 2020 Termedia Sp. z o. o.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License ( http://creativecommons.org/licenses/by-nc-sa/4.0/)

                History
                : 23 March 2020
                : 09 May 2020
                Categories
                Original Paper

                microrna,myocardial infarction,mir-126,mir-1
                microrna, myocardial infarction, mir-126, mir-1

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