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      Circulating miR-1254 predicts ventricular remodeling in patients with ST-Segment-Elevation Myocardial Infarction: A cardiovascular magnetic resonance study

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          Abstract

          Reliable noninvasive prognostic biomarkers for left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) are needed. This study aimed to evaluate a panel of circulating microRNAs (miRNAs) as biomarkers of LV remodeling using cardiovascular magnetic resonance (CMR). We prospectively evaluated patients with a first STEMI treated with primary percutaneous coronary intervention who underwent CMR imaging at 1 week and 6 months after STEMI (n = 70). miRNAs were measured using PCR-based technologies in plasma samples collected at admission. The associations between miRNAs and LV diastolic and systolic volumes, and ejection fraction at 6-months were estimated in adjusted models. Median age was 60 years, 71.4% were male. miR-1254 was significantly associated in univariate analyses. Patients in the highest tertile of miR-1254 exhibited lower values of LVEDVI and LVESVI and higher values of LVEF at 1 week. After comprehensive multivariate adjustment including clinical, CMR variables, hs-troponin-T and NT-proBNP, miRNA-1254 was associated with decreasing LVESVI (P = 0.006), and borderline negative associated with LVEDVI (P = 0.063) at 6-months. miR-1254 also exhibited a significant positive association with increasing LVEF during follow-up (P < 0.001). Plasma miRNA-1254 predicted changes in LV volumes and LVEF at 6 months after STEMI. The value of miR-1254 to inform tailored treatment selection and monitor ongoing efficacy deserves further investigation.

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          Roles for microRNAs in conferring robustness to biological processes.

          Biological systems use a variety of mechanisms to maintain their functions in the face of environmental and genetic perturbations. Increasing evidence suggests that, among their roles as posttranscriptional repressors of gene expression, microRNAs (miRNAs) help to confer robustness to biological processes by reinforcing transcriptional programs and attenuating aberrant transcripts, and they may in some network contexts help suppress random fluctuations in transcript copy number. These activities have important consequences for normal development and physiology, disease, and evolution. Here, we will discuss examples and principles of miRNAs that contribute to robustness in animal systems. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Universal definition of myocardial infarction.

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              Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives

              Recent research has demonstrated that the non-coding genome plays a key role in genetic programming and gene regulation during development as well as in health and cardiovascular disease. About 99% of the human genome do not encode proteins, but are transcriptionally active representing a broad spectrum of non-coding RNAs (ncRNAs) with important regulatory and structural functions. Non-coding RNAs have been identified as critical novel regulators of cardiovascular risk factors and cell functions and are thus important candidates to improve diagnostics and prognosis assessment. Beyond this, ncRNAs are rapidly emgerging as fundamentally novel therapeutics. On a first level, ncRNAs provide novel therapeutic targets some of which are entering assessment in clinical trials. On a second level, new therapeutic tools were developed from endogenous ncRNAs serving as blueprints. Particularly advanced is the development of RNA interference (RNAi) drugs which use recently discovered pathways of endogenous short interfering RNAs and are becoming versatile tools for efficient silencing of protein expression. Pioneering clinical studies include RNAi drugs targeting liver synthesis of PCSK9 resulting in highly significant lowering of LDL cholesterol or targeting liver transthyretin (TTR) synthesis for treatment of cardiac TTR amyloidosis. Further novel drugs mimicking actions of endogenous ncRNAs may arise from exploitation of molecular interactions not accessible to conventional pharmacology. We provide an update on recent developments and perspectives for diagnostic and therapeutic use of ncRNAs in cardiovascular diseases, including atherosclerosis/coronary disease, post-myocardial infarction remodelling, and heart failure.
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                Author and article information

                Contributors
                thum.thomas@mh-hannover.de
                abayesgenis@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                11 October 2018
                11 October 2018
                2018
                : 8
                : 15115
                Affiliations
                [1 ]ISNI 0000 0000 9529 9877, GRID grid.10423.34, Institute of Molecular and Translational Therapeutic Strategies (IMTTS), , Hannover Medical School, ; Hannover, Germany
                [2 ]ISNI 0000 0004 1794 1077, GRID grid.420258.9, Institute of Biomedical Research of Barcelona (IIBB) - Spanish National Research Council (CSIC), ; Barcelona, Spain
                [3 ]ISNI 0000 0000 9314 1427, GRID grid.413448.e, CIBERCV, Institute of Health Carlos III, ; Madrid, Spain
                [4 ]Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
                [5 ]ISNI 0000 0004 1767 6330, GRID grid.411438.b, Heart Institute, , Hospital Universitari Germans Trias i Pujol, ; Badalona, Barcelona Spain
                [6 ]GRID grid.7080.f, Department of Medicine, , CIBERCV Autonomous University of Barcelona, ; Badalona, Spain
                [7 ]GRID grid.411308.f, Cardiology Department, , Hospital Clínico Universitario, INCLIVA, Departamento de Medicina, CIBERCV Universitat València, ; València, Spain
                [8 ]GRID grid.429186.0, Heart Failure and Cardiac Regeneration (ICREC) Research Program, , Health Science Research Institute Germans Trias i Pujol (IGTP), ; Badalona, Spain
                [9 ]ISNI 0000 0004 1770 5832, GRID grid.157927.f, Universitat Politècnica de València, ; València, Spain
                [10 ]ISNI 0000 0000 9529 9877, GRID grid.10423.34, REBIRTH Excellence Cluster, , Hannover Medical School, ; Hannover, Germany
                [11 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Imperial College London, , National Heart and Lung Institute, ; London, UK
                Article
                33491
                10.1038/s41598-018-33491-y
                6181905
                30310086
                a0e4c739-c8ce-4db8-b571-40c87248132e
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 July 2018
                : 25 September 2018
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