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Wang X, Lu Y, Zhao R, Zhu B, Liu J, Yue Q, Wu R, Han S, Gao Y, Chen J, Gong J, He D, Xu T, Ying J. Global surveillance of circulating microRNA for diagnostic and prognostic assessment of acute myocardial infarction based on the plasma small RNA sequencing. Biomark Res 2024; 12:143. [PMID: 39563415 DOI: 10.1186/s40364-024-00690-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 11/13/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Circulating microRNAs (miRNAs) are recently a rapidly increasing of interest as non-invasive biomarkers for diagnosis and prognosis of acute myocardial infarction (AMI). Previous studies revealed that several miRNAs exhibited the capacity for diagnosis and prognosis of AMI, the reasons why these circulating miRNAs are concerned as targets for investigation are quite cryptogenic, presumably due to the lack of clues provided by global surveillance at the transcriptome level, and the current data for some miRNAs are controversial and inconsistent among independent studies. METHODS To comprehensively profiling the potential miRNAs for diagnosis and prognosis of AMI, we reported transcriptomes of circulating miRNAs in the plasma of 27 healthy controls, 64 AMI patients (37 STEMI and 27 NSTEMI) and 20 AMI patients who were subjected to reperfusion therapy. Meanwhile, the cTnI of AMI patients was parallel determined. Differentially-circulated miRNAs were analyzed between each group. All detected circulating miRNAs were examined by ROC analysis and then LASSO dimension reduction to obtain an optimal panel for diagnosis of AMI. A five-year period follow-up towards the AMI and reperfusion patients was performed, and the prognostic value of circulating miRNAs in these patients was estimated by using the Cox regression model, ROC and Kaplan-Meier curves. RESULTS Comprehensive global differences of miRNAs transcriptome among AMI, reperfusion patients and healthy controls were identified. A total of 40 miRNAs, called high diagnostic performance miRNAs, including several previous well-studied miRNAs with AUC greater than 0.85 were shown to discriminate AMI with healthy controls. In addition, 29 miRNAs were analyzed to be strongly correlated with the plasma cTnI level, of which 20 overlapped with high diagnostic performance miRNAs. These overlapped miRNAs are over-represented in the pathways which actually reflect the pathological cause of myocardial infarction, as well as the regulation of gene expression and energetic pathway of cellular response to hypoxia. Finally, two miRNAs were analyzed to be significantly correlated to all-cause mortality. CONCLUSION This is the first time to survey plasma miRNAs for the development of AMI diagnostic and prognostic biomarkers at the transcriptome level. A subset of miRNAs exhibited potential diagnostic and prognostic merits for AMI.
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Affiliation(s)
- Xiaomin Wang
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
- Institute of Translational Medicine, Baotou Central Hospital, Baotou, China
| | - Yaojun Lu
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
| | - Ruiping Zhao
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
- Institute of Translational Medicine, Baotou Central Hospital, Baotou, China
| | - Bing Zhu
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
- Institute of Translational Medicine, Baotou Central Hospital, Baotou, China
| | - Jian Liu
- Dian Diagnostics Group Co., Ltd, Hangzhou, China
| | - Qiang Yue
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
| | - Rina Wu
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
| | - Shuwen Han
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
| | - Yuanyuan Gao
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
| | - Juan Chen
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
| | - Jie Gong
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
| | - Danna He
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China
| | - Teng Xu
- Department of Cardiology/Chest Pain Center, Baotou Central Hospital, Baotou, China.
- Institute of Translational Medicine, Baotou Central Hospital, Baotou, China.
| | - Jianchao Ying
- Wenzhou Key Laboratory of Emergency, Critical Care, and Disaster Medicine/Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
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Dawkins S, Digby JE, Belgard TG, Lee R, De Maria GL, Banning AP, Kharbanda RK, Mayr M, Choudhury RP, Channon KM. Stratification of acute myocardial and endothelial cell injury, salvage index and final infarct size by systematic microRNA profiling in acute ST-elevation myocardial infarction. Coron Artery Dis 2024; 35:122-134. [PMID: 38009375 DOI: 10.1097/mca.0000000000001284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2023]
Abstract
AIM Acute injury and subsequent remodelling responses to ST-segment elevation myocardial infarction (STEMI) are major determinants of clinical outcome. Current imaging and plasma biomarkers provide delayed readouts of myocardial injury and recovery. Here, we sought to systematically characterize all microRNAs (miRs) released during the acute phase of STEMI and relate miR release to magnetic resonance imaging (MRI) findings to predict acute and late responses to STEMI, from a single early blood sample. METHODS AND RESULTS miRs were quantified in blood samples obtained from patients after primary PCI (PPCI) for STEMI. Cardiac MRI (cMRI) was performed to quantify myocardial edema, infarct size and salvage index. Regression models were constructed to predict these outcomes measures, which were then tested with a validation cohort. Transcoronary miR release was quantified from paired measurements of coronary artery and coronary sinus samples. A cell culture model was used to identify endothelial cell-derived miRs.A total of 72 patients undergoing PPCI for acute STEMI underwent miR analysis and cMRI. About >200 miRs were detectable in plasma after STEMI, from which 128 miRs were selected for quantification in all patients. Known myocardial miRs demonstrated a linear correlation with troponin release, and these increased across the transcoronary gradient. We identified novel miRs associated with microvascular injury and myocardial salvage. Regression models were constructed using a training cohort, then tested in a validation cohort, and predicted myocardial oedema, infarct size and salvage index. CONCLUSION Analysis of miR release after STEMI identifies biomarkers that predict both acute and late outcomes after STEMI. A novel miR-based biomarker score enables the estimation of area at risk, late infarct size and salvage index from a single blood sample 6 hours after PPCI, providing a simple and rapid alternative to serial cMRI characterization of STEMI outcome.
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Affiliation(s)
- Sam Dawkins
- Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Janet E Digby
- Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | | | - Regent Lee
- Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Giovanni Luigi De Maria
- Oxford Heart Centre, National Institute for Health (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford
| | - Adrian P Banning
- Oxford Heart Centre, National Institute for Health (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford
| | - Rajesh K Kharbanda
- Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
- Oxford Heart Centre, National Institute for Health (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford
| | - Manuel Mayr
- King's British Heart Foundation Centre, King's College London, London, UK
| | - Robin P Choudhury
- Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
- Oxford Heart Centre, National Institute for Health (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford
| | - Keith M Channon
- Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
- Oxford Heart Centre, National Institute for Health (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford
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Asjad E, Dobrzynski H. MicroRNAs: Midfielders of Cardiac Health, Disease and Treatment. Int J Mol Sci 2023; 24:16207. [PMID: 38003397 PMCID: PMC10671258 DOI: 10.3390/ijms242216207] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 11/05/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023] Open
Abstract
MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play a role in post-transcriptional gene regulation. It is generally accepted that their main mechanism of action is the negative regulation of gene expression, through binding to specific regions in messenger RNA (mRNA) and repressing protein translation. By interrupting protein synthesis, miRNAs can effectively turn genes off and influence many basic processes in the body, such as developmental and apoptotic behaviours of cells and cardiac organogenesis. Their importance is highlighted by inhibiting or overexpressing certain miRNAs, which will be discussed in the context of coronary artery disease, atrial fibrillation, bradycardia, and heart failure. Dysregulated levels of miRNAs in the body can exacerbate or alleviate existing disease, and their omnipresence in the body makes them reliable as quantifiable markers of disease. This review aims to provide a summary of miRNAs as biomarkers and their interactions with targets that affect cardiac health, and intersperse it with current therapeutic knowledge. It intends to succinctly inform on these topics and guide readers toward more comprehensive works if they wish to explore further through a wide-ranging citation list.
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Affiliation(s)
- Emman Asjad
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK;
| | - Halina Dobrzynski
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK;
- Department of Anatomy, Jagiellonian University Medical College, 31-034 Krakow, Poland
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Matute-Blanco L, Fernández-Rodríguez D, Casanova-Sandoval J, Belmonte T, Benítez ID, Rivera K, Garcia-Guimaraes M, Cortés Villar C, Peral Disdier V, Millán Segovia R, Barriuso I, de Gonzalo-Calvo D, Barbé F, Worner F. Study protocol for the epigenetic characterization of angor pectoris according to the affected coronary compartment: Global and comprehensive assessment of the relationship between invasive coronary physiology and microRNAs. PLoS One 2023; 18:e0283097. [PMID: 37167303 PMCID: PMC10174526 DOI: 10.1371/journal.pone.0283097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 03/01/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) are noncoding RNAs involved in post-transcriptional genetic regulation with a proposed role in intercellular communication. miRNAs are considered promising biomarkers in ischemic heart disease. Invasive physiological evaluation allows a precise assessment of each affected coronary compartment. Although some studies have associated the expression of circulating miRNAs with invasive physiological indexes, their global relationship with coronary compartments has not been assessed. Here, we will evaluate circulating miRNAs profiles according to the coronary pattern of the vascular compartment affectation. STUDY AND DESIGN This is an investigator-initiated, multicentre, descriptive study to be conducted at three centres in Spain (NCT05374694). The study will include one hundred consecutive patients older than 18 years with chest pain of presumed coronary cause undergoing invasive physiological evaluation, including fractional flow reserve (FFR) and index of microvascular resistance (IMR). Patients will be initially classified into four groups, according to FFR and IMR: macrovascular and microvascular affectation (FFR≤0.80 / IMR≥25), isolated macrovascular affectation (FFR≤0.80 / IMR<25), isolated microvascular affectation (FFR>0.80 / IMR ≥25) and normal coronary indexes (FFR>0.80 / IMR<25). Patients with isolated microvascular affectation or normal indexes will also undergo the acetylcholine test and may be reclassified as a fifth group in the presence of spasm. A panel of miRNAs previously associated with molecular mechanisms linked to chronic coronary syndrome will be analysed using RT-qPCR. CONCLUSIONS The results of this study will identify miRNA profiles associated with patterns of coronary affectation and will contribute to a better understanding of the mechanistic pathways of coronary pathology.
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Affiliation(s)
- Lucía Matute-Blanco
- Department of Cardiology, Institut de Reçerca Biomèdica de Lleida (IRBLleida), University Hospital Arnau de Vilanova, Lleida, Spain
| | - Diego Fernández-Rodríguez
- Department of Cardiology, Institut de Reçerca Biomèdica de Lleida (IRBLleida), University Hospital Arnau de Vilanova, Lleida, Spain
| | - Juan Casanova-Sandoval
- Department of Cardiology, Institut de Reçerca Biomèdica de Lleida (IRBLleida), University Hospital Arnau de Vilanova, Lleida, Spain
| | - Thalía Belmonte
- Institut de Reçerca Biomèdica de Lleida (IRBLleida), Translational Research in Respiratory Medicine Group, Lleida, Spain
- Institute of Health Carlos III, CIBER of Respiratory Diseases (CIBERES), Madrid, Spain
| | - Iván D. Benítez
- Institut de Reçerca Biomèdica de Lleida (IRBLleida), Translational Research in Respiratory Medicine Group, Lleida, Spain
- Institute of Health Carlos III, CIBER of Respiratory Diseases (CIBERES), Madrid, Spain
| | - Kristian Rivera
- Department of Cardiology, Institut de Reçerca Biomèdica de Lleida (IRBLleida), University Hospital Arnau de Vilanova, Lleida, Spain
| | - Marcos Garcia-Guimaraes
- Department of Cardiology, Institut de Reçerca Biomèdica de Lleida (IRBLleida), University Hospital Arnau de Vilanova, Lleida, Spain
| | | | | | - Raúl Millán Segovia
- Department of Cardiology, University Hospital Son Espases, Palma de Mallorca, Spain
| | - Ignacio Barriuso
- Department of Cardiology, Institut de Reçerca Biomèdica de Lleida (IRBLleida), University Hospital Arnau de Vilanova, Lleida, Spain
| | - David de Gonzalo-Calvo
- Institut de Reçerca Biomèdica de Lleida (IRBLleida), Translational Research in Respiratory Medicine Group, Lleida, Spain
- Institute of Health Carlos III, CIBER of Respiratory Diseases (CIBERES), Madrid, Spain
| | - Ferran Barbé
- Institut de Reçerca Biomèdica de Lleida (IRBLleida), Translational Research in Respiratory Medicine Group, Lleida, Spain
- Institute of Health Carlos III, CIBER of Respiratory Diseases (CIBERES), Madrid, Spain
| | - Fernando Worner
- Department of Cardiology, Institut de Reçerca Biomèdica de Lleida (IRBLleida), University Hospital Arnau de Vilanova, Lleida, Spain
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Venugopal P, George M, Kandadai SD, Balakrishnan K, Uppugunduri CRS. Prioritization of microRNA biomarkers for a prospective evaluation in a cohort of myocardial infarction patients based on their mechanistic role using public datasets. Front Cardiovasc Med 2022; 9:981335. [PMID: 36407428 PMCID: PMC9668885 DOI: 10.3389/fcvm.2022.981335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 10/11/2022] [Indexed: 11/06/2022] Open
Abstract
Background MicroRNAs (miR) have proven to be promising biomarkers for several diseases due to their diverse functions, stability and tissue/organ-specific nature. Identification of new markers with high sensitivity and specificity will help in risk reduction in acute myocardial infarction (AMI) patients with chest pain and also prevent future adverse outcomes. Hence the aim of this study was to perform a detailed in silico analysis for identifying the mechanistic role of miRs involved in the pathogenesis/prognosis of AMI for prospective evaluation in AMI patients. Methods miR profiling data was extracted from GSE148153 and GSE24591 datasets using the GEO2R gene expression omnibus repository and analyzed using limma algorithm. Differentially expressed miRs were obtained by comparing MI patients with corresponding controls after multiple testing corrections. Data mining for identifying candidate miRs from published literature was also performed. Target prediction and gene enrichment was done using standard bioinformatics tools. Disease specific analysis was performed to identify target genes specific for AMI using open targets platform. Protein-protein interaction and pathway analysis was done using STRING database and Cytoscape platform. Results and conclusion The analysis revealed significant miRs like let-7b-5p, let-7c-5p, miR-4505, and miR-342-3p in important functions/pathways including phosphatidylinositol-3-kinase/AKT and the mammalian target of rapamycin, advanced glycation end products and its receptor and renin–angiotensin–aldosterone system by directly targeting angiotensin II receptor type 1, forkhead box protein O1, etc. With this approach we were able to prioritize the miR candidates for a prospective clinical association study in AMI patients of south Indian origin.
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Affiliation(s)
| | - Melvin George
- Clinical Research Department, Hindu Mission Hospital, Chennai, India
| | | | | | - Chakradhara Rao S. Uppugunduri
- CANSEARCH Research Platform in Pediatric Oncology and Hematology, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland
- *Correspondence: Chakradhara Rao S. Uppugunduri,
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6
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Evans PC, Davidson SM, Wojta J, Bäck M, Bollini S, Brittan M, Catapano AL, Chaudhry B, Cluitmans M, Gnecchi M, Guzik TJ, Hoefer I, Madonna R, Monteiro JP, Morawietz H, Osto E, Padró T, Sluimer JC, Tocchetti CG, Van der Heiden K, Vilahur G, Waltenberger J, Weber C. From novel discovery tools and biomarkers to precision medicine-basic cardiovascular science highlights of 2021/22. Cardiovasc Res 2022; 118:2754-2767. [PMID: 35899362 PMCID: PMC9384606 DOI: 10.1093/cvr/cvac114] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 05/13/2022] [Accepted: 06/07/2022] [Indexed: 11/16/2022] Open
Abstract
Here, we review the highlights of cardiovascular basic science published in 2021 and early 2022 on behalf of the European Society of Cardiology Council for Basic Cardiovascular Science. We begin with non-coding RNAs which have emerged as central regulators cardiovascular biology, and then discuss how technological developments in single-cell 'omics are providing new insights into cardiovascular development, inflammation, and disease. We also review recent discoveries on the biology of extracellular vesicles in driving either protective or pathogenic responses. The Nobel Prize in Physiology or Medicine 2021 recognized the importance of the molecular basis of mechanosensing and here we review breakthroughs in cardiovascular sensing of mechanical force. We also summarize discoveries in the field of atherosclerosis including the role of clonal haematopoiesis of indeterminate potential, and new mechanisms of crosstalk between hyperglycaemia, lipid mediators, and inflammation. The past 12 months also witnessed major advances in the field of cardiac arrhythmia including new mechanisms of fibrillation. We also focus on inducible pluripotent stem cell technology which has demonstrated disease causality for several genetic polymorphisms in long-QT syndrome and aortic valve disease, paving the way for personalized medicine approaches. Finally, the cardiovascular community has continued to better understand COVID-19 with significant advancement in our knowledge of cardiovascular tropism, molecular markers, the mechanism of vaccine-induced thrombotic complications and new anti-viral therapies that protect the cardiovascular system.
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Affiliation(s)
| | | | | | | | - Sveva Bollini
- Department of Experimental Medicine (DIMES), University of Genova, L.go R. Benzi 10, 16132 Genova, Italy
| | - Mairi Brittan
- Queens Medical Research Institute, BHF Centre for Cardiovascular Sciences, University of Edinburgh, Scotland
| | | | - Bill Chaudhry
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Matthijs Cluitmans
- Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands
- Philips Research, Eindhoven, Netherlands
| | - Massimiliano Gnecchi
- Department of Molecular Medicine, Unit of Cardiology, University of Pavia Division of Cardiology, Unit of Translational Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Medicine, University of Cape Town, South Africa
| | - Tomasz J Guzik
- Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland and Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Imo Hoefer
- Central Diagnostic Laboratory, UMC Utrecht, the Netherlands
| | - Rosalinda Madonna
- Institute of Cardiology, Department of Surgical, Medical, Molecular and Critical Care Area, University of Pisa, Pisa, 56124 Italy
- Department of Internal Medicine, Cardiology Division, University of Texas Medical School, Houston, TX, USA
| | - João P Monteiro
- Queens Medical Research Institute, BHF Centre for Cardiovascular Sciences, University of Edinburgh, Scotland
| | - Henning Morawietz
- Division of Vascular Endothelium and Microcirculation, Department of Medicine III, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
| | - Elena Osto
- Institute of Clinical Chemistry and Department of Cardiology, Heart Center, University Hospital & University of Zurich, Switzerland
| | - Teresa Padró
- Cardiovascular Program-ICCC, IR-Hospital Santa Creu i Sant Pau, IIB-Sant Pau, and CIBERCV-Instituto de Salud Carlos III, Barcelona, Spain
| | - Judith C Sluimer
- Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, Netherland
- University/BHF Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK
| | - Carlo Gabriele Tocchetti
- Cardio-Oncology Unit, Department of Translational Medical Sciences, Center for Basic and Clinical Immunology (CISI), Interdepartmental Center of Clinical and Translational Sciences (CIRCET), Interdepartmental Hypertension Research Center (CIRIAPA), Federico II University, 80131 Napoli, Italy
| | - Kim Van der Heiden
- Biomedical Engineering, Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Gemma Vilahur
- Cardiovascular Program-ICCC, IR-Hospital Santa Creu i Sant Pau, IIB-Sant Pau, and CIBERCV-Instituto de Salud Carlos III, Barcelona, Spain
| | - Johannes Waltenberger
- Cardiovascular Medicine, Medical Faculty, University of Muenster, Muenster, Germany
- Diagnostic and Therapeutic Heart Center, Zurich, Switzerland
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Stătescu C, Anghel L, Tudurachi BS, Leonte A, Benchea LC, Sascău RA. From Classic to Modern Prognostic Biomarkers in Patients with Acute Myocardial Infarction. Int J Mol Sci 2022; 23:9168. [PMID: 36012430 PMCID: PMC9409468 DOI: 10.3390/ijms23169168] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 08/09/2022] [Accepted: 08/11/2022] [Indexed: 11/17/2022] Open
Abstract
Despite all the important advances in its diagnosis and treatment, acute myocardial infarction (AMI) is still one of the most prominent causes of morbidity and mortality worldwide. Early identification of patients at high risk of poor outcomes through the measurement of various biomarker concentrations might contribute to more accurate risk stratification and help to guide more individualized therapeutic strategies, thus improving prognoses. The aim of this article is to provide an overview of the role and applications of cardiac biomarkers in risk stratification and prognostic assessment for patients with myocardial infarction. Although there is no ideal biomarker that can provide prognostic information for risk assessment in patients with AMI, the results obtained in recent years are promising. Several novel biomarkers related to the pathophysiological processes found in patients with myocardial infarction, such as inflammation, neurohormonal activation, myocardial stress, myocardial necrosis, cardiac remodeling and vasoactive processes, have been identified; they may bring additional value for AMI prognosis when included in multi-biomarker strategies. Furthermore, the use of artificial intelligence algorithms for risk stratification and prognostic assessment in these patients may have an extremely important role in improving outcomes.
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Affiliation(s)
- Cristian Stătescu
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I. M. Georgescu”, 700503 Iași, Romania
- Internal Medicine Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700503 Iași, Romania
| | - Larisa Anghel
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I. M. Georgescu”, 700503 Iași, Romania
- Internal Medicine Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700503 Iași, Romania
| | - Bogdan-Sorin Tudurachi
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I. M. Georgescu”, 700503 Iași, Romania
| | - Andreea Leonte
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I. M. Georgescu”, 700503 Iași, Romania
| | - Laura-Cătălina Benchea
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I. M. Georgescu”, 700503 Iași, Romania
| | - Radu-Andy Sascău
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I. M. Georgescu”, 700503 Iași, Romania
- Internal Medicine Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700503 Iași, Romania
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8
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miR-133a-A Potential Target for Improving Cardiac Mitochondrial Health and Regeneration After Injury. J Cardiovasc Pharmacol 2022; 80:187-193. [PMID: 35500168 DOI: 10.1097/fjc.0000000000001279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 04/01/2022] [Indexed: 11/26/2022]
Abstract
ABSTRACT The various roles of muscle secretory factors and myokines have been well studied, but in recent decades, the role of myocyte-specific microRNAs (myomiRs) has gained momentum. These myomiRs are known to play regulatory roles in muscle health in general, both skeletal muscle and cardiac muscle. In this review, we have focused on the significance of a myomiR termed miR-133a in cardiovascular health. The available literature supports the claim that miR-133a could be helpful in the healing process of muscle tissue after injury. The protective function could be due to its regulatory effect on muscle or stem cell mitochondrial function. In this review, we have shed light on the protective mechanisms offered by miR-133a. Most of the beneficial effects are due to the presence of miR-133a in circulation or tissue-specific expression. We have also reviewed the potential mechanisms by which miR-133a could interact with cell surface receptors and also transcriptional mechanisms by which they offer cardioprotection and regeneration. Understanding these mechanisms will help in finding an ideal strategy to repair cardiac tissue after injury.
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9
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Venugopal P, Balakrishnan K, Damal Kandadai S, George M. Usefullness of MicroRNAs in Predicting the Clinical Outcome of Patients with Acute Myocardial Infarction During Follow-Up: A Systematic Review. Genet Test Mol Biomarkers 2022; 26:277-289. [PMID: 35638909 DOI: 10.1089/gtmb.2021.0283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: Myocardial infarction (MI) is reported as the leading cause of mortality and morbidity worldwide. It is associated with a 30% mortality rate. Echocardiography, coronary angiography, and biomarkers like cardiac troponins are employed as prognostic tests. Although these biomarkers are the gold standard for the diagnosis of MI, they are not accurate as prognostic markers due to their lack of specificity. Studies have suggested that dysregulation of specific microRNAs (miRNAs) influences post-MI complications during follow-up. However, the findings of these studies have several inconsistencies. This systematic review was performed to investigate the potential of miRNAs to predict clinical outcomes post-MI. Methodology: Pubmed and Google Scholar databases were used for identifying research articles published from inception till August 2021; the search terms included "microRNAs" AND "prognosis" AND "myocardial infarction" or "acute coronary syndrome." All the articles included were critically analyzed using STROBE guidelines. Results and Conclusion: Several miRNAs were elevated in MI patients, including miR-208b, miR-499, and miR-375. Association of these miRNA levels with the outcome of MI, such as all-cause mortality and major adverse cardiovascular events during follow-up, were also reported. However, none of the studies included in this systematic review exhibited promising evidence that these miRNAs can be utilized as ideal biomarkers for prognosis post-MI. Understanding the molecular mechanisms involved in the pathogenesis and progression of MI is crucial. Hence, these findings can be used as a guide when performing further experimental studies to identify useful post-MI prognostic markers.
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Affiliation(s)
| | | | | | - Melvin George
- Department of Clinical Research, Hindu Mission Hospital, Chennai, India
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10
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Exploring Endothelial Colony-Forming Cells to Better Understand the Pathophysiology of Disease: An Updated Review. Stem Cells Int 2022; 2022:4460041. [PMID: 35615696 PMCID: PMC9126670 DOI: 10.1155/2022/4460041] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 04/20/2022] [Accepted: 05/09/2022] [Indexed: 12/12/2022] Open
Abstract
Endothelial cell (EC) dysfunction has been implicated in a variety of pathological conditions. The collection of ECs from patients is typically conducted postmortem or through invasive procedures, such as surgery and interventional procedures, hampering efforts to clarify the role of ECs in disease onset and progression. In contrast, endothelial colony-forming cells (ECFCs), also termed late endothelial progenitor cells, late outgrowth endothelial cells, blood outgrowth endothelial cells, or endothelial outgrowth cells, are obtained in a minimally invasive manner, namely, by the culture of human peripheral blood mononuclear cells in endothelial growth medium. ECFCs resemble mature ECs phenotypically, genetically, and functionally, making them excellent surrogates for ECs. Numerous studies have been performed that examined ECFC function in conditions such as coronary artery disease, diabetes mellitus, hereditary hemorrhagic telangiectasia, congenital bicuspid aortic valve disease, pulmonary arterial hypertension, venous thromboembolic disease, and von Willebrand disease. Here, we provide an updated review of studies using ECFCs that were performed to better understand the pathophysiology of disease. We also discuss the potential of ECFCs as disease biomarkers and the standardized methods to culture, quantify, and evaluate ECFCs and suggest the future direction of research in this field.
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11
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Wang H, Liu H, Zhao X, Chen X. Heterogeneous nuclear ribonucleoprotein U-actin complex derived from extracellular vesicles facilitates proliferation and migration of human coronary artery endothelial cells by promoting RNA polymerase II transcription. Bioengineered 2022; 13:11469-11486. [PMID: 35535400 PMCID: PMC9276035 DOI: 10.1080/21655979.2022.2066754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Coronary artery disease (CAD) represents a fatal public threat. The involvement of extracellular vesicles (EVs) in CAD has been documented. This study explored the regulation of embryonic stem cells (ESCs)-derived EVs-hnRNPU-actin complex in human coronary artery endothelial cell (HCAEC) growth. Firstly, in vitro HCAEC hypoxia models were established. EVs were extracted from ESCs by ultracentrifugation. HCAECs were treated with EVs and si-VEGF for 24 h under hypoxia, followed by assessment of cell proliferation, apoptosis, migration, and tube formation. Uptake of EVs by HCAECs was testified. Additionally, hnRNPU, VEGF, and RNA Pol II levels were determined using Western blotting and CHIP assays. Interaction between hnRNPU and actin was evaluated by Co-immunoprecipitation assay. HCAEC viability and proliferation were lowered, apoptosis was enhanced, wound fusion was decreased, and the number of tubular capillary structures was reduced under hypoxia, whereas ESC-EVs treatment counteracted these effects. Moreover, EVs transferred hnRNPU into HCAECs. EVs-hnRNPU-actin complex increased RNA Pol II level on the VEGF gene promoter and promoted VEGF expression in HCAECs. Inhibition of hnRNPU or VEGF both annulled the promotion of EVs on HCAEC growth. Collectively, ESC-EVs-hnRNPU-actin increased RNA Pol II phosphorylation and VEGF expression, thus promoting HCAEC growth.
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Affiliation(s)
- Han Wang
- Department of Cardiovascular, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Hengdao Liu
- Department of Cardiovascular, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xi Zhao
- Department of Cardiovascular, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xiaowei Chen
- Department of Cardiovascular, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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12
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Tanase DM, Gosav EM, Ouatu A, Badescu MC, Dima N, Ganceanu-Rusu AR, Popescu D, Floria M, Rezus E, Rezus C. Current Knowledge of MicroRNAs (miRNAs) in Acute Coronary Syndrome (ACS): ST-Elevation Myocardial Infarction (STEMI). Life (Basel) 2021; 11:life11101057. [PMID: 34685428 PMCID: PMC8541211 DOI: 10.3390/life11101057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 10/02/2021] [Accepted: 10/06/2021] [Indexed: 02/06/2023] Open
Abstract
Regardless of the newly diagnostic and therapeutic advances, coronary artery disease (CAD) and more explicitly, ST-elevation myocardial infarction (STEMI), remains one of the leading causes of morbidity and mortality worldwide. Thus, early and prompt diagnosis of cardiac dysfunction is pivotal in STEMI patients for a better prognosis and outcome. In recent years, microRNAs (miRNAs) gained attention as potential biomarkers in myocardial infarction (MI) and acute coronary syndromes (ACS), as they have key roles in heart development, various cardiac processes, and act as indicators of cardiac damage. In this review, we describe the current available knowledge about cardiac miRNAs and their functions, and focus mainly on their potential use as novel circulating diagnostic and prognostic biomarkers in STEMI.
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Affiliation(s)
- Daniela Maria Tanase
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (D.M.T.); (A.O.); (M.C.B.); (N.D.); (A.R.G.-R.); (D.P.); (C.R.)
- Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania
| | - Evelina Maria Gosav
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (D.M.T.); (A.O.); (M.C.B.); (N.D.); (A.R.G.-R.); (D.P.); (C.R.)
- Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania
- Correspondence: (E.M.G.); (M.F.); (E.R.)
| | - Anca Ouatu
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (D.M.T.); (A.O.); (M.C.B.); (N.D.); (A.R.G.-R.); (D.P.); (C.R.)
- Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania
| | - Minerva Codruta Badescu
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (D.M.T.); (A.O.); (M.C.B.); (N.D.); (A.R.G.-R.); (D.P.); (C.R.)
- Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania
| | - Nicoleta Dima
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (D.M.T.); (A.O.); (M.C.B.); (N.D.); (A.R.G.-R.); (D.P.); (C.R.)
- Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania
| | - Ana Roxana Ganceanu-Rusu
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (D.M.T.); (A.O.); (M.C.B.); (N.D.); (A.R.G.-R.); (D.P.); (C.R.)
- Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania
| | - Diana Popescu
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (D.M.T.); (A.O.); (M.C.B.); (N.D.); (A.R.G.-R.); (D.P.); (C.R.)
- Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania
| | - Mariana Floria
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (D.M.T.); (A.O.); (M.C.B.); (N.D.); (A.R.G.-R.); (D.P.); (C.R.)
- Internal Medicine Clinic, Emergency Military Clinical Hospital Iasi, 700483 Iasi, Romania
- Correspondence: (E.M.G.); (M.F.); (E.R.)
| | - Elena Rezus
- Department of Rheumatology and Physiotherapy, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- I Rheumatology Clinic, Clinical Rehabilitation Hospital, 700661 Iasi, Romania
- Correspondence: (E.M.G.); (M.F.); (E.R.)
| | - Ciprian Rezus
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (D.M.T.); (A.O.); (M.C.B.); (N.D.); (A.R.G.-R.); (D.P.); (C.R.)
- Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania
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Hromadka M, Motovska Z, Hlinomaz O, Kala P, Tousek F, Jarkovsky J, Beranova M, Jansky P, Svoboda M, Krepelkova I, Rokyta R, Widimsky P, Karpisek M. MiR-126-3p and MiR-223-3p as Biomarkers for Prediction of Thrombotic Risk in Patients with Acute Myocardial Infarction and Primary Angioplasty. J Pers Med 2021; 11:jpm11060508. [PMID: 34199723 PMCID: PMC8230013 DOI: 10.3390/jpm11060508] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/17/2021] [Accepted: 05/31/2021] [Indexed: 12/12/2022] Open
Abstract
Aim. This study was designed to evaluate the relationship between microRNAs (miRNAs), miR-126-3p and miR-223-3p, as new biomarkers of platelet activation, and predicting recurrent thrombotic events after acute myocardial infarction (AMI). Methods and Results. The analysis included 598 patients randomized in the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI). The measurements of miRNAs were performed by using a novel miRNA immunoassay method. The association of miRNAs with the occurrence of the ischemic endpoint (EP) (cardiovascular death, nonfatal MI, or stroke) and bleeding were analyzed. The miR-223-3p level was significantly related to an increased risk of occurrence of the ischemic EP within 30 days (odds ratio (OR) = 15.74, 95% confidence interval (CI): 2.07-119.93, p = 0.008) and one year (OR = 3.18, 95% CI: 1.40-7.19, p = 0.006), respectively. The miR-126-3p to miR-223-3p ratio was related to a decreased risk of occurrence of EP within 30 days (OR = 0.14, 95% CI: 0.03-0.61, p = 0.009) and one year (OR = 0.37, 95% CI: 0.17-0.82, p = 0.014), respectively. MiRNAs were identified as independent predictors of EP even after adjustment for confounding clinical predictors. Adding miR-223-3p and miR-126-3p to miR-223-3p ratios as predictors into the model calculating the ischemic risk significantly increased the predictive accuracy for combined ischemic EP within one year more than using only clinical ischemic risk parameters. No associations between miRNAs and bleeding complications were identified. Conclusion. The miR-223-3p and the miR-126-3p are promising independent predictors of thrombotic events and can be used for ischemic risk stratification after AMI.
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Affiliation(s)
- Milan Hromadka
- Department of Cardiology, University Hospital and Faculty of Medicine in Pilsen, Charles University, 304 60 Pilsen, Czech Republic; (M.H.); (R.R.)
| | - Zuzana Motovska
- Cardiocentre, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, 100 34 Prague, Czech Republic;
- Correspondence: ; Tel.: +420-267-163-760; Fax: +420-267-163-763
| | - Ota Hlinomaz
- First Department of Internal Medicine—Cardioangiology, International Clinical Research Center, Faculty of Medicine, Masaryk University and St. Anne’s University Hospital, 656 91 Brno, Czech Republic; (O.H.); (M.B.)
| | - Petr Kala
- Department of Internal Medicine and Cardiology, University Hospital and Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic;
| | - Frantisek Tousek
- Cardiocentre—Department of Cardiology, Regional Hospital, 370 01 Ceske Budejovice, Czech Republic;
| | - Jiri Jarkovsky
- Institute of Biostatistics and Analyses at the Faculty of Medicine and the Faculty of Science, Masaryk University, 602 00 Brno, Czech Republic; (J.J.); (M.S.)
| | - Marketa Beranova
- First Department of Internal Medicine—Cardioangiology, International Clinical Research Center, Faculty of Medicine, Masaryk University and St. Anne’s University Hospital, 656 91 Brno, Czech Republic; (O.H.); (M.B.)
| | - Pavel Jansky
- Department of Anestesiology and Resuscitation, University Hospital Kralovske Vinohrady, 100 34 Prague, Czech Republic;
| | - Michal Svoboda
- Institute of Biostatistics and Analyses at the Faculty of Medicine and the Faculty of Science, Masaryk University, 602 00 Brno, Czech Republic; (J.J.); (M.S.)
| | - Iveta Krepelkova
- BioVendor—Laboratory Medicine, 621 00 Brno, Czech Republic; (I.K.); (M.K.)
- Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, 621 00 Brno, Czech Republic
| | - Richard Rokyta
- Department of Cardiology, University Hospital and Faculty of Medicine in Pilsen, Charles University, 304 60 Pilsen, Czech Republic; (M.H.); (R.R.)
| | - Petr Widimsky
- Cardiocentre, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, 100 34 Prague, Czech Republic;
| | - Michal Karpisek
- BioVendor—Laboratory Medicine, 621 00 Brno, Czech Republic; (I.K.); (M.K.)
- Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, 621 00 Brno, Czech Republic
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14
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Scărlătescu AI, Micheu MM, Popa-Fotea NM, Dorobanțu M. MicroRNAs in Acute ST Elevation Myocardial Infarction-A New Tool for Diagnosis and Prognosis: Therapeutic Implications. Int J Mol Sci 2021; 22:4799. [PMID: 33946541 PMCID: PMC8124280 DOI: 10.3390/ijms22094799] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/23/2021] [Accepted: 04/26/2021] [Indexed: 02/07/2023] Open
Abstract
Despite diagnostic and therapeutic advances, coronary artery disease and especially its extreme manifestation, ST elevation myocardial infarction (STEMI), remain the leading causes of morbidity and mortality worldwide. Early and prompt diagnosis is of great importance regarding the prognosis of STEMI patients. In recent years, microRNAs (miRNAs) have emerged as promising tools involved in many pathophysiological processes in various fields, including cardiovascular diseases. In acute coronary syndromes (ACS), circulating levels of miRNAs are significantly elevated, as an indicator of cardiac damage, making them a promising marker for early diagnosis of myocardial infarction. They also have prognostic value and great potential as therapeutic targets considering their key function in gene regulation. This review aims to summarize current information about miRNAs and their role as diagnostic, prognostic and therapeutic targets in STEMI patients.
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Affiliation(s)
- Alina Ioana Scărlătescu
- Department of Cardiology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.-M.P.-F.); (M.D.)
- Department of Cardiology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania;
| | - Miruna Mihaela Micheu
- Department of Cardiology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania;
| | - Nicoleta-Monica Popa-Fotea
- Department of Cardiology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.-M.P.-F.); (M.D.)
- Department of Cardiology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania;
| | - Maria Dorobanțu
- Department of Cardiology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.-M.P.-F.); (M.D.)
- Department of Cardiology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania;
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15
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Cruz MS, da Silva AMG, de Souza KSC, Luchessi AD, Silbiger VN. miRNAs emerge as circulating biomarkers of post-myocardial infarction heart failure. Heart Fail Rev 2021; 25:321-329. [PMID: 31254148 DOI: 10.1007/s10741-019-09821-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Heart failure (HF) is a clinical syndrome that involves structural changes in the heart, leading to a decrease in cardiac output, mainly caused by myocardial infarction (MI), which is the most common form of cardiovascular disease worldwide. Clinical evaluation remains the most accurate diagnostic method for ischemic HF, since the known biomarkers have high cost, are difficult to use for early diagnosis, and have low specificity. This often leads to late diagnosis since only ~ 25% symptoms of HF appear after MI. Studies suggest that small non-coding RNAs (miRNAs) play an important role in the regulation of this pathophysiological process and are, therefore, important targets in the discovery of non-invasive biomarkers for HF. Thus, the aim of this review was to identify circulating miRNAs (plasma, serum, and whole blood) described for post-MI HF patients. This review covered 19 experimental studies on humans, which investigated the relationship between circulating miRNAs and the development, monitoring, or prognosis of ischemic HF. This analysis was aimed at proposing potential targets for HF and the future application of miRNAs as HF biomarkers.
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Affiliation(s)
- Marina Sampaio Cruz
- Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | | | - Karla Simone Costa de Souza
- Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - André Ducati Luchessi
- Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Vivian Nogueira Silbiger
- Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
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16
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Liu Y, Li Y, Li J, Zuo X, Cao Q, Xie W, Wang H. Inhibiting miR‑1 attenuates pulmonary arterial hypertension in rats. Mol Med Rep 2021; 23:283. [PMID: 33604679 PMCID: PMC7905329 DOI: 10.3892/mmr.2021.11922] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 01/27/2021] [Indexed: 12/21/2022] Open
Abstract
MicroRNAs (miRs) are reported to serve key roles in pulmonary arterial hypertension (PAH). miR-1 has been found in cardiovascular diseases. The present study aimed to determine whether the knockdown of miR-1 could inhibit right ventricle (RV) remodeling and thereby control PAH in model rats. PAH model rats were established by exposing rats to hypoxia, while cardiac fibroblasts (CFs) obtained from PAH model rats were treated with hypoxia to establish an in vitro model, and RV remodeling was evaluated by Masson staining and the levels of collagen I, collagen III, α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) evaluated by western blotting or reverse transcription-quantitative PCR. The results revealed that the expression levels of miR-1 were upregulated in the RV of PAH model rats induced with hypoxia and in the CFs treated with hypoxia. The mean pulmonary arterial pressure, RV systolic pressure, RV/(left ventricle + interventricular septum) and RV/tibia length were increased in PAH rats; however, the increases in all parameters were subsequently reversed by transfection with a miR-1 antagomiR in PAH model rats. The transfection with the miR-1 antagomiR inhibited the development of RV fibrosis and downregulated the mRNA expression levels of collagen I, collagen III, α-SMA and CTGF in the RV tissue of PAH model rats. The upregulation of collagen I, collagen III, α-SMA and CTGF expression levels in hypoxia-treated CFs was also subsequently reversed by miR-1 antagomiR transfection. The expression levels of collagen I, collagen III, α-SMA and CTGF were also upregulated in the CFs obtained from PAH model rats, and these increases were attenuated by miR-1 antagomiR transfection. The expression levels of phosphorylated (p)-PI3K and p-AKT were also upregulated in hypoxia-treated CFs, and these increases were also inhibited by transfection with miR-1 antagomiR. In conclusion, these results indicated that inhibiting miR-1 may attenuate RV hypertrophy and fibrosis in PAH model rats, a mechanism that may involve the PI3K/AKT signaling pathway.
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Affiliation(s)
- Yun Liu
- Department of Intensive Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Yong Li
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Jinhai Li
- Department of Intensive Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Xiangrong Zuo
- Department of Intensive Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Quan Cao
- Department of Intensive Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Weiping Xie
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Hong Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
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17
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Role of Selected miRNAs as Diagnostic and Prognostic Biomarkers in Cardiovascular Diseases, Including Coronary Artery Disease, Myocardial Infarction and Atherosclerosis. J Cardiovasc Dev Dis 2021; 8:jcdd8020022. [PMID: 33669699 PMCID: PMC7923109 DOI: 10.3390/jcdd8020022] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 02/13/2021] [Accepted: 02/15/2021] [Indexed: 02/08/2023] Open
Abstract
Cardiovascular diseases are the leading cause of death worldwide in different cohorts. It is well known that miRNAs have a crucial role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. MiRNAs also have been reported to be associated with cardiac reactions, leading to myocardial infarction (MCI) and ultimately heart failure (HF). To prevent these heart diseases, proper and timely diagnosis of cardiac dysfunction is pivotal. Though there are many symptoms associated with an irregular heart condition and though there are some biomarkers available that may indicate heart disease, authentic, specific and sensitive markers are the need of the hour. In recent times, miRNAs have proven to be promising candidates in this regard. They are potent biomarkers as they can be easily detected in body fluids (blood, urine, etc.) due to their remarkable stability and presence in apoptotic bodies and exosomes. Existing studies suggest the role of miRNAs as valuable biomarkers. A single biomarker may be insufficient to diagnose coronary artery disease (CAD) or acute myocardial infarction (AMI); thus, a combination of different miRNAs may prove fruitful. Therefore, this review aims to highlight the role of circulating miRNA as diagnostic and prognostic biomarkers in cardiovascular diseases such as coronary artery disease (CAD), myocardial infarction (MI) and atherosclerosis.
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18
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Kaur A, Mackin ST, Schlosser K, Wong FL, Elharram M, Delles C, Stewart DJ, Dayan N, Landry T, Pilote L. Systematic review of microRNA biomarkers in acute coronary syndrome and stable coronary artery disease. Cardiovasc Res 2021; 116:1113-1124. [PMID: 31782762 DOI: 10.1093/cvr/cvz302] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 10/24/2019] [Accepted: 11/26/2019] [Indexed: 01/03/2023] Open
Abstract
The aim of this systematic review was to assess dysregulated miRNA biomarkers in coronary artery disease (CAD). Dysregulated microRNA (miRNAs) have been shown to be linked to cardiovascular pathologies including CAD and may have utility as diagnostic and prognostic biomarkers. We compared miRNAs identified in acute coronary syndrome (ACS) compared with stable CAD and control populations. We conducted a systematic search of controlled vocabulary and free text terms related to ACS, stable CAD and miRNA in Biosis Previews (OvidSP), The Cochrane Library (Wiley), Embase (OvidSP), Global Health (OvidSP), Medline (PubMed and OvidSP), Web of Science (Clarivate Analytics), and ClinicalTrials.gov which yielded 7370 articles. Of these, 140 original articles were appropriate for data extraction. The most frequently reported miRNAs in any CAD (miR-1, miR-133a, miR-208a/b, and miR-499) are expressed abundantly in the heart and play crucial roles in cardiac physiology. In studies comparing ACS cases with stable CAD patients, miR-21, miR-208a/b, miR-133a/b, miR-30 family, miR-19, and miR-20 were most frequently reported to be dysregulated in ACS. While a number of miRNAs feature consistently across studies in their expression in both ACS and stable CAD, when compared with controls, certain miRNAs were reported as biomarkers specifically in ACS (miR-499, miR-1, miR-133a/b, and miR-208a/b) and stable CAD (miR-215, miR-487a, and miR-502). Thus, miR-21, miR-133, and miR-499 appear to have the most potential as biomarkers to differentiate the diagnosis of ACS from stable CAD, especially miR-499 which showed a correlation between the level of their concentration gradient and myocardial damage. Although these miRNAs are potential diagnostic biomarkers, these findings should be interpreted with caution as the majority of studies conducted predefined candidate-driven assessments of a limited number of miRNAs (PROSPERO registration: CRD42017079744).
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Affiliation(s)
- Amanpreet Kaur
- Centre for Outcomes Research and Evaluation, Research Institute, McGill University Health Centre, 5252 de Maisonneuve West, 2B.39, Montreal QC H4A 3S5, Canada
| | - Sharon T Mackin
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Kenny Schlosser
- Ottawa Hospital Research Institute and Faculty of Medicine, University of Ottawa, Ottawa, Canada
| | - Fui Lin Wong
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Malik Elharram
- Department of Medicine, McGill University Health Centre, Montreal, Canada
| | - Christian Delles
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Duncan J Stewart
- Ottawa Hospital Research Institute and Faculty of Medicine, University of Ottawa, Ottawa, Canada
| | - Natalie Dayan
- Centre for Outcomes Research and Evaluation, Research Institute, McGill University Health Centre, 5252 de Maisonneuve West, 2B.39, Montreal QC H4A 3S5, Canada.,Department of Medicine, McGill University Health Centre, Montreal, Canada
| | - Tara Landry
- Medical Library, Montreal General Hospital, McGill University Health Centre, Montreal, Canada
| | - Louise Pilote
- Centre for Outcomes Research and Evaluation, Research Institute, McGill University Health Centre, 5252 de Maisonneuve West, 2B.39, Montreal QC H4A 3S5, Canada.,Department of Medicine, McGill University Health Centre, Montreal, Canada
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19
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Spinka G, Bartko PE, Pavo N, Freitag C, Zlabinger K, Prausmüller S, Arfsten H, Heitzinger G, Mascherbauer J, Hengstenberg C, Gyöngyösi M, Hülsmann M, Goliasch G. Secondary mitral regurgitation-Insights from microRNA assessment. Eur J Clin Invest 2021; 51:e13381. [PMID: 32780418 PMCID: PMC7900984 DOI: 10.1111/eci.13381] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/01/2020] [Accepted: 08/07/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND While secondary mitral regurgitation (sMR) is associated with adverse outcome in heart failure with reduced ejection fraction (HFrEF), key pathophysiologic mechanisms remain poorly understood and might be elucidated by microRNAs (miRNA/miR), that were recently related to cardiac remodelling. This study sought to assess (i) the differences of miRNA profiles in patients with severe sMR compared to matched disease controls, (ii) the correlation between circulating miRNAs and surrogates of sMR severity as well as (iii) the prognostic implications of miRNA levels in severe sMR. MATERIALS AND METHODS Sixty-six HFrEF patients were included, of these 44 patients with severe sMR 2:1 matched to HFrEF controls with no/mild sMR. A comprehensive set of miRNAs (miR-21, miR-29a, miR-122, miR-132, miR-133a, miR-let7i) were measured and correlated to echocardiographic sMR severity. RESULTS miRNA patterns differed distinctly between patients with severe sMR and HFrEF controls (P < .05). Among the panel of assessed miRNAs, miR-133a correlated most strongly with surrogates of sMR severity (r = -0.41, P = .001 with sMR vena contracta width). Interestingly, elevated levels of miR-133 were associated with an increased risk for cardiovascular death and/or HF hospitalizations with and adjusted HR of 1.85 (95% CI 1.24-2.76, P = .003). CONCLUSIONS This study unveils distinct pathophysiologic maladaptions at a cellular level in patients with severe sMR compared to no/mild sMR by showing significant differences in miRNA profiles and correlations with sMR severity, supporting the concept that sMR drives cardiac remodelling in heart failure. Moreover, the increased risk for adverse outcome in HFrEF patients with severe sMR conveyed by miR-133a might indicate irreversible myocardial damage.
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Affiliation(s)
- Georg Spinka
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Philipp E Bartko
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Noemi Pavo
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Claudia Freitag
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Katrin Zlabinger
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Suriya Prausmüller
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Henrike Arfsten
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Gregor Heitzinger
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Julia Mascherbauer
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | | | - Mariann Gyöngyösi
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Martin Hülsmann
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Georg Goliasch
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
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20
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Bostan MM, Stătescu C, Anghel L, Șerban IL, Cojocaru E, Sascău R. Post-Myocardial Infarction Ventricular Remodeling Biomarkers-The Key Link between Pathophysiology and Clinic. Biomolecules 2020; 10:E1587. [PMID: 33238444 PMCID: PMC7700609 DOI: 10.3390/biom10111587] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 11/13/2020] [Accepted: 11/18/2020] [Indexed: 02/07/2023] Open
Abstract
Studies in recent years have shown increased interest in developing new methods of evaluation, but also in limiting post infarction ventricular remodeling, hoping to improve ventricular function and the further evolution of the patient. This is the point where biomarkers have proven effective in early detection of remodeling phenomena. There are six main processes that promote the remodeling and each of them has specific biomarkers that can be used in predicting the evolution (myocardial necrosis, neurohormonal activation, inflammatory reaction, hypertrophy and fibrosis, apoptosis, mixed processes). Some of the biomarkers such as creatine kinase-myocardial band (CK-MB), troponin, and N-terminal-pro type B natriuretic peptide (NT-proBNP) were so convincing that they immediately found their place in the post infarction patient evaluation protocol. Others that are related to more complex processes such as inflammatory biomarkers, atheroma plaque destabilization biomarkers, and microRNA are still being studied, but the results so far are promising. This article aims to review the markers used so far, but also the existing data on new markers that could be considered, taking into consideration the most important studies that have been conducted so far.
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Affiliation(s)
- Maria-Madălina Bostan
- Internal Medicine Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700503 Iasi, Romania; (M.-M.B.); (R.S.)
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I.M.Georgescu”, 700503 Iasi, Romania
| | - Cristian Stătescu
- Internal Medicine Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700503 Iasi, Romania; (M.-M.B.); (R.S.)
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I.M.Georgescu”, 700503 Iasi, Romania
| | - Larisa Anghel
- Internal Medicine Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700503 Iasi, Romania; (M.-M.B.); (R.S.)
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I.M.Georgescu”, 700503 Iasi, Romania
| | | | - Elena Cojocaru
- Department of Morphofunctional Sciences I—Pathology, “Grigore T. Popa” University of Medicine and Pharmacy, 700503 Iasi, Romania;
| | - Radu Sascău
- Internal Medicine Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700503 Iasi, Romania; (M.-M.B.); (R.S.)
- Cardiology Department, Cardiovascular Diseases Institute “Prof. Dr. George I.M.Georgescu”, 700503 Iasi, Romania
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21
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Hu Y, Xiong J, Wen H, Wei H, Zeng X. MiR-98-5p promotes ischemia/reperfusion-induced microvascular dysfunction by targeting NGF and is a potential biomarker for microvascular reperfusion. Microcirculation 2020; 28:e12657. [PMID: 32892409 DOI: 10.1111/micc.12657] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 08/18/2020] [Accepted: 08/26/2020] [Indexed: 12/29/2022]
Abstract
OBJECTIVE This study examined the correlation between serum miR-98-5p levels and indices of microvascular reperfusion in patients undergoing primary percutaneous coronary intervention (pPCI) after ST-segment elevation myocardial infarction (STEMI). Additionally, we evaluated the mechanisms by which miR-98-5p promoted ischemia/reperfusion (I/R)-induced injury in both cultured cell lines and an animal model. METHODS Circulating miR-98-5p levels were measured and compared from 171 STEMI patients undergoing pPCI, who were divided into two groups: no-reflow and reflow. The levels of miR-98-5p, nerve growth factor (NGF), and transient receptor potential vanilloid 1 (TRPV1) were analyzed in cultured human coronary endothelial cells (HCECs) exposed to hypoxia/reoxygenation (H/R). The effects of antagomir-98-5p on myocardial I/R-induced microvascular dysfunction in vivo were evaluated. Target gene expression and activity were assessed. RESULTS Higher miR-98-5p levels were associated with compromised indices of microvascular reperfusion. In vitro experiments on HCECs showed that exposure to H/R significantly increased miR-98-5p levels. We identified NGF as a novel target of miR-98-5p. Further, antagomir-98-5p relieved microvascular dysfunction and enhanced the expression of NGF and TRPV1 in the rat myocardial I/R model. CONCLUSIONS MiR-98-5p promotes microvascular dysfunction by targeting the NGF-TRPV1 axis. Serum miR-98-5p serves as a potential biomarker for microvascular reperfusion.
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Affiliation(s)
- Yisen Hu
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi, P.R. China
| | - Jingjie Xiong
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi, P.R. China
| | - Hong Wen
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi, P.R. China
| | - Heng Wei
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi, P.R. China
| | - Xiaocong Zeng
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi, P.R. China
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22
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Inhibition of microRNA-146a attenuated heart failure in myocardial infarction rats. Biosci Rep 2020; 39:221324. [PMID: 31763669 PMCID: PMC6928527 DOI: 10.1042/bsr20191732] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 11/15/2019] [Accepted: 11/22/2019] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to determine the roles of microRNA (miR)-146a on myocardial infarction (MI)-induced heart failure and cardiac remodeling. Experiments were carried out in Sprague-Dawley rats treated with ligation of left coronary artery to induce heart failure, and in primary neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes treated with angiotensin (Ang) II. Four weeks after MI, rats were injected with miR-146a antagomiR or agomiR via tail vein. After 2 weeks of injection, the rats were killed. In MI rats, left ventricle (LV) ejection fraction and fractional shortening were reduced, and LV volumes in diastole and systole were increased, which were reversed by miR-146a antagomiR, and further exacerbated after miR-146a agomiR treatment. Administration of miR-146a antagomiR improved the decreases of LV ±dp/dtmax and LV systolic pressure (LVSP), and the increase in LV end-diastolic pressure (LVEDP) of MI rats, but miR-146a agomiR deteriorated the LV ±dp/dtmax, LVSP and LVEDP. The increases in the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen I and collagen III in the heart, and ST2 and norepinephrine in the serum of MI rats were inhibited by miR-146a antagomiR, but aggravated after miR-146a agomiR treatment. The increases of collagen I and collagen III levels induced by Ang II in CFs, and the increases of ANP and BNP levels induced by Ang II in cardiomyocytes were inhibited by miR-146a antagomiR, but aggravated by miR-146a agomiR. These results demonstrated that inhibition of miR-146a improved cardiac dysfunction and cardiac remodeling in heart failure rats.
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23
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Coelho-Lima J, Mohammed A, Cormack S, Jones S, Ali A, Panahi P, Barter M, Bagnall A, Ali S, Young D, Spyridopoulos I. Kinetics Analysis of Circulating MicroRNAs Unveils Markers of Failed Myocardial Reperfusion. Clin Chem 2020; 66:247-256. [PMID: 31672851 DOI: 10.1373/clinchem.2019.308353] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 09/17/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Failed myocardial reperfusion occurs in approximately 50% of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). It manifests as microvascular obstruction (MVO) on cardiac magnetic resonance (CMR) imaging. Although prognostically important, MVO is not routinely screened for. Our aim was to investigate the kinetics of circulating short noncoding ribonucleic acids [microRNAs (miRNAs)] following PPCI and their association with MVO in STEMI patients. METHODS Screening of 2083 miRNAs in plasma from STEMI patients with (n = 6) and without (n = 6) MVO was performed by next-generation sequencing. Two candidate miRNAs were selected and quantified at 13 time points within 3 h postreperfusion in 20 STEMI patients by reverse transcription and quantitative PCR. Subsequently, these 2 miRNAs were measured in a "validation" STEMI cohort (n = 50) that had CMR imaging performed at baseline and 3 months post-PPCI to evaluate their association with MVO. RESULTS miR-1 and miR-133b were rapidly released following PPCI in a monophasic or biphasic pattern. Both miRNAs were enriched in circulating microparticles. A second miR-1 peak (90-180 min postreperfusion) seemed to be associated with a higher index of microvascular resistance. In addition, miR-1 and miR-133b levels at 90 min post-PPCI were approximately 3-fold (P = 0.001) and 4.4-fold (P = 0.008) higher in patients with MVO, respectively. Finally, miR-1 was significantly increased in a subgroup of patients with worse left ventricular (LV) functional recovery 3 months post-PPCI. CONCLUSIONS miR-1 and miR-133b levels increase within 3 h of PPCI. They are positively associated with MVO and worse LV functional recovery post-PPCI.
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Affiliation(s)
- Jose Coelho-Lima
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Ashfaq Mohammed
- Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, UK
| | - Suzanne Cormack
- Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, UK
| | - Samuel Jones
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Adnan Ali
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Pedram Panahi
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Matt Barter
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Alan Bagnall
- Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, UK.,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Simi Ali
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - David Young
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Ioakim Spyridopoulos
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.,Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, UK
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24
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Wexler Y, Nussinovitch U. The Diagnostic Value of Mir-133a in ST Elevation and Non-ST Elevation Myocardial Infarction: A Meta-Analysis. Cells 2020; 9:cells9040793. [PMID: 32218383 PMCID: PMC7226415 DOI: 10.3390/cells9040793] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 03/20/2020] [Accepted: 03/23/2020] [Indexed: 12/27/2022] Open
Abstract
Numerous studies have reported correlations between plasma microRNA signatures and cardiovascular disease. MicroRNA-133a (Mir-133a) has been researched extensively for its diagnostic value in acute myocardial infarction (AMI). While initial results seemed promising, more recent studies cast doubt on the diagnostic utility of Mir-133a, calling its clinical prospects into question. Here, the diagnostic potential of Mir-133a was analyzed using data from multiple papers. Medline, Embase, and Web of Science were systematically searched for publications containing “Cardiovascular Disease”, “MicroRNA”, “Mir-133a” and their synonyms. Diagnostic performance was assessed using area under the summary receiver operator characteristic curve (AUC), while examining the impact of age, sex, final diagnosis, and time. Of the 753 identified publications, 9 were included in the quantitative analysis. The pooled AUC for Mir-133a was 0.73. Analyses performed separately on studies using healthy vs. symptomatic controls yielded pooled AUCs of 0.89 and 0.68, respectively. Age and sex were not found to significantly affect diagnostic performance. Our findings indicate that control characteristics and methodological inconsistencies are likely the causes of incongruent reports, and that Mir-133a may have limited use in distinguishing symptomatic patients from those suffering AMI. Lastly, we hypothesized that Mir-133a may find a new use as a risk stratification biomarker in patients with specific subsets of non-ST elevation myocardial infarction (NSTEMI).
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Affiliation(s)
- Yehuda Wexler
- Rappaport Faculty of Medicine and Research Institute, Technion - Israel Institute of Technology, POB 9649, Haifa 3109601, Israel;
| | - Udi Nussinovitch
- Applicative Cardiovascular Research Center (ACRC) and Department of Cardiology, Meir Medical Center, Kfar Saba 44281, Israel
- Correspondence: ; Tel.: +972-53-526-8535
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25
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Yang X, Du X, Ma K, Li G, Liu Z, Rong W, Miao H, Zhu F, Cui Q, Wu S, Li Y, Du J. Circulating miRNAs Related to Long-term Adverse Cardiovascular Events in STEMI Patients: A Nested Case-Control Study. Can J Cardiol 2020; 37:77-85. [PMID: 32735867 DOI: 10.1016/j.cjca.2020.03.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Revised: 03/11/2020] [Accepted: 03/16/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Long-term morbidity and mortality of patients with ST-segment-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI) remain substantial. Circulating microRNAs (miRNAs) play an important role in cardiovascular disease development. We aimed to identify circulating miRNAs associated with adverse cardiovascular events after acute myocardial infarction (AMI). METHODS We performed a prospective, nested, case-control study of 932 patients with STEMI who underwent primary PCI. A 3-phase approach was conducted to screen candidate circulating miRNAs in 70 patients who subsequently experienced cardiac death, hospitalization for heart failure, or recurrent AMI (major adverse cardiovascular events [MACE] group) and in 140 patients matched for age, sex, time from symptom onset to blood collection and dual-antiplatelet therapy who did not report adverse cardiovascular events during 2-year follow-up (non-MACE group). RESULTS We found that miR-26a-5p, miR-21-5p, and miR-191-5p levels were lower in the MACE group than in the non-MACE group (all P < 0.001). Multivariate conditional logistic regression analysis revealed that miR-26a-5p, miR-21-5p, and miR-191-5p levels were significantly inversely associated with incident primary composite outcomes (all adjusted P < 0.01). Importantly, the combination of these 3 miRNAs plus B-type natriuretic peptide clearly improved the risk scores recommended in the current guidelines, as determined with the use of C-statistics, net reclassification, and integrated discrimination. CONCLUSIONS Our study provides proof-of-concept in humans that circulating miRNAs are associated with increased rates of distinct cardiovascular events, suggesting that they can serve as effective prognostic biomarkers and therapeutic targets for patients with AMI.
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Affiliation(s)
- Xinying Yang
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Key Laboratory of Remodelling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China; Beijing Collaborative Innovative Research Centre for Cardiovascular Diseases, Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
| | - Xiaoyu Du
- First Hospital of Jilin University, Changchun, China
| | - Ke Ma
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Key Laboratory of Remodelling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China; Beijing Collaborative Innovative Research Centre for Cardiovascular Diseases, Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
| | - Guoqi Li
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Key Laboratory of Remodelling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China; Beijing Collaborative Innovative Research Centre for Cardiovascular Diseases, Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
| | - Zhuohui Liu
- Tongmei Group General Hospital, Datong, China
| | - Wei Rong
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Key Laboratory of Remodelling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China; Beijing Collaborative Innovative Research Centre for Cardiovascular Diseases, Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
| | - Huangtai Miao
- Emergency and Critical Care Centre, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Fuli Zhu
- Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Qinghua Cui
- Department of Biomedical Informatics, Department of Physiology and Pathophysiology, Centre for Noncoding RNA Medicine, MOE Key Laboratory of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Shaowei Wu
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
| | - Yulin Li
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Key Laboratory of Remodelling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China; Beijing Collaborative Innovative Research Centre for Cardiovascular Diseases, Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
| | - Jie Du
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Key Laboratory of Remodelling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China; Beijing Collaborative Innovative Research Centre for Cardiovascular Diseases, Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
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26
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Escate R, Padró T, Suades R, Camino S, Muñiz O, Diaz-Diaz JL, Sionis A, Mata P, Badimon L. High miR-133a levels in the circulation anticipates presentation of clinical events in familial hypercholesterolaemia patients. Cardiovasc Res 2020; 117:109-122. [PMID: 32061123 DOI: 10.1093/cvr/cvaa039] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Revised: 11/17/2019] [Accepted: 02/10/2020] [Indexed: 12/12/2022] Open
Abstract
AIMS Presentation of acute events in patients with atherosclerosis remains unpredictable even after controlling for classical risk factors. MicroRNAs (miRNAs) measured in liquid biopsies could be good candidate biomarkers to improve risk prediction. Here, we hypothesized that miRNAs could predict atherosclerotic plaque progression and clinical event presentation in familial hypercholesterolaemia (FH) patients. METHODS AND RESULTS Circulating miRNAs (plasma, exosomes, and microvesicles) were investigated by TaqMan Array and RT-qPCR assays. Patients with genetic diagnosis of FH and healthy relatives from the SAFEHEART cohort were included. A differential signature of 10 miRNA was obtained by comparing two extreme phenotypes consisting of FH patients suffering a cardiovascular event (CVE) within a 8-year follow-up period (FH-CVE, N = 42) and non-FH hypercholesterolaemic relatives from the same cohort, matched for age and treatment, without CVE during the same period (nFH-nCVE, N = 30). The validation studies included two independent groups of patients with FH background (discovery group, N = 89, validation group N = 196), developing a future CVE (FH-CVE) or not (FH-nCVE) within the same time period of follow-up. Of the 10 miRNAs initially selected, miR-133a was significantly higher in FH-CVE than in FH-nCVE patients. Receiver operating characteristic analysis confirmed miR-133a as the best microRNA for predicting CVE in FH patients (0.76 ± 0.054; P < 0.001). Furthermore, Kaplan-Meier and COX analysis showed that high plasma miR-133a levels associated to the higher risk of presenting a CVE within the next 8 years (hazard ratio 3.89, 95% confidence interval 1.88-8.07; P < 0.001). In silico analysis of curate biological interactions related miR-133a with target genes involved in regulation of the cell-membrane lipid-receptor LRP6 and inflammatory cytokines (CXCL8, IL6, and TNF). These predictions were experimentally proven in human macrophages and endothelial cells transfected with agomiR-133a. CONCLUSION Elevated levels of miR-133a in the circulation anticipate those FH patients that are going to present a clinical CVE within the next 2 years (average). Mechanistically, miR-133a is directly related with lipid- and inflammatory signalling in key cells for atherosclerosis progression.
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Affiliation(s)
- Rafael Escate
- Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.,Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain
| | - Teresa Padró
- Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.,Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain
| | - Rosa Suades
- Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain
| | - Sandra Camino
- Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain
| | - Ovidio Muñiz
- Servicio de Medicina Interna, Hospital Virgen del Rocío, Sevilla, España, Spain
| | | | - Alessandro Sionis
- Cardiology Department, Acute and Intensive Cardiac Care Unit, Hospital Santa Creu i Sant Pau, Barcelona, Spain
| | - Pedro Mata
- Fundación Hipercolesterolemia Familiar, Madrid, Spain
| | - Lina Badimon
- Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.,Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain.,Cardiovascular Research Chair, UAB, Barcelona, Spain
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27
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Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D, Suciu N, Cretoiu SM, Voinea SC. miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells 2020; 9:E276. [PMID: 31979244 PMCID: PMC7072450 DOI: 10.3390/cells9020276] [Citation(s) in RCA: 816] [Impact Index Per Article: 163.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 01/14/2020] [Accepted: 01/21/2020] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.
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Affiliation(s)
- Carmen Elena Condrat
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Dana Claudia Thompson
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Madalina Gabriela Barbu
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Oana Larisa Bugnar
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Andreea Boboc
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Dragos Cretoiu
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
| | - Nicolae Suciu
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
- Division of Obstetrics, Gynecology and Neonatology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
- Department of Obstetrics and Gynecology, Polizu Clinical Hospital, Alessandrescu-Rusescu National Institute for Mother and Child Health, 020395 Bucharest, Romania
| | - Sanda Maria Cretoiu
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
| | - Silviu Cristian Voinea
- Department of Surgical Oncology, Prof. Dr. Alexandru Trestioreanu Oncology Institute, Carol Davila University of Medicine and Pharmacy, 252 Fundeni Rd., 022328 Bucharest, Romania;
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Thankam FG, Agrawal DK. Infarct Zone: a Novel Platform for Exosome Trade in Cardiac Tissue Regeneration. J Cardiovasc Transl Res 2020; 13:686-701. [PMID: 31907784 DOI: 10.1007/s12265-019-09952-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 12/27/2019] [Indexed: 12/13/2022]
Abstract
The global incidence of coronary artery diseases (CADs), especially myocardial infarction (MI), has drastically increased in recent years. Even though the conventional therapies have improved the outcomes, the post-MI complications and the increased rate of recurrence among the survivors are still alarming. Molecular events associated with the pathogenesis and the adaptive responses of the surviving myocardium are largely unknown. Focus on exosome-mediated signaling for cell-cell/matrix communications at the infarct zone reflects an emerging opportunity in cardiac regeneration. Also, cardiac tissue engineering provides promising insights for the next generation of therapeutic approaches in the management of CADs. In this article, we critically reviewed the current understanding on the biology of cardiac exosomes, therapeutic potential of exosomes, and recent developments in cardiac tissue engineering and discussed novel translational approaches based on tissue engineering and exosomes for cardiac regeneration and CADs.
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Affiliation(s)
- Finosh G Thankam
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA
| | - Devendra K Agrawal
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA.
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Abstract
Chronic heart failure, diabetes, depression, and other chronic diseases are associated with high mortality rate and low cure rate. Exercise induces muscle contraction and secretes multiple myokines, which affects the signaling pathways in skeletal muscle tissues and regulate remote organ functions. Exercise is known to be effective in treating a variety of chronic diseases. Here we summarize how exercise influences skeletal muscle, heart, brain, gut, and liver, and prevents heart failure, cognitive dysfunction, obesity, fatty liver, and other diseases. Exercise training may achieve additional benefits as compared to the present medication for these chronic diseases through cross talk among skeletal muscle and other organs.
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Affiliation(s)
- Zhiqing Fan
- Department of Cardiology, Daqing Qilfield General Hospital, Daqing, China
| | - Minjun Xu
- Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, China
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30
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Barraclough JY, Joan M, Joglekar MV, Hardikar AA, Patel S. MicroRNAs as Prognostic Markers in Acute Coronary Syndrome Patients-A Systematic Review. Cells 2019; 8:cells8121572. [PMID: 31817254 PMCID: PMC6952952 DOI: 10.3390/cells8121572] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 11/23/2019] [Accepted: 12/02/2019] [Indexed: 01/09/2023] Open
Abstract
Background: The potential utility of microRNAs (miRNAs) in the diagnosis, prognosis, and treatment of multiple disease states has been an area of great interest since their discovery. In patients with cardiovascular disease, there is a large pool of literature amassed from the last decade assessing their diagnostic and prognostic potential. This systematic review sought to determine whether existing literature supports the use of miRNAs as prognostic markers after an Acute Coronary Syndrome (ACS) presentation. Methods: A systematic review of published articles from 2005–2019 using MEDLINE and EMBASE databases was undertaken independently by two reviewers. Studies addressing prognosis in an ACS population yielded 32 studies and 2 systematic reviews. Results/conclusion: 23 prospective studies reported significant differences in miRNA levels and 16 compared the predictive power of miRNAs. The most common miRNAs assessed included miR-133a, -208b, -21, -1, -34a, -150, and -423, shown to be involved in cell differentiation, apoptosis, and angiogenesis. Barriers to the use of miRNAs as prognostic markers include bias in miRNA selection, small sample size, variable normalization of data, and adjustment for confounders. Therefore, findings from this systematic review do not support the use of miRNAs for prognostication post-ACS beyond traditional cardiovascular risk factors, existing risk scores, and stratifications tools.
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Affiliation(s)
- Jennifer Y Barraclough
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney 2050, Australia
- Sydney Medical School, The University of Sydney, Sydney 2050, Australia
- Heart Research Institute, Sydney 2042, Australia
| | - Michelyn Joan
- Sydney Medical School, The University of Sydney, Sydney 2050, Australia
| | - Mugdha V Joglekar
- NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney 2050, Australia
| | - Anandwardhan A Hardikar
- NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney 2050, Australia
| | - Sanjay Patel
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney 2050, Australia
- Sydney Medical School, The University of Sydney, Sydney 2050, Australia
- Heart Research Institute, Sydney 2042, Australia
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31
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Wernly B, Fuernau G, Masyuk M, Muessig JM, Pfeiler S, Bruno RR, Desch S, Muench P, Lichtenauer M, Kelm M, Adams V, Thiele H, Eitel I, Jung C. Syndecan-1 Predicts Outcome in Patients with ST-Segment Elevation Infarction Independent from Infarct-related Myocardial Injury. Sci Rep 2019; 9:18367. [PMID: 31797997 PMCID: PMC6892872 DOI: 10.1038/s41598-019-54937-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 11/13/2019] [Indexed: 12/23/2022] Open
Abstract
Syndecan-1 (sdc1) is a surface protein part of the endothelial glycocalyx (eGC). Soluble sdc1 is derived from shedding and indicates damaged eGC. We assessed the predictive value of plasma sdc1 concentrations for future cardiovascular events in acute reperfused ST-segment elevation myocardial infarction (STEMI) patients. A total of 206 patients admitted for STEMI were included in this study (29% female; age 65 ± 12 years) and followed-up for six months. Plasma samples were obtained post-intervention and analyzed for sdc1 by Enzyme-linked Immunosorbent Assay (ELISA). Primary outcome was six-month-mortality. Sdc1 did not correlate with biomarkers such as creatine kinase (CK) (r = 0.11; p = 0.01) or troponin (r = −0.12; p = 0.09), nor with infarct size (r = −0.04; p = 0.67) and myocardial salvage index (r = 0.11; p = 0.17). Sdc-1 was associated with mortality (changes per 100 ng/mL sdc-1 concentration; HR 1.08 95% 1.03–1.12; p = 0.001). An optimal cut-off was calculated at >120 ng/mL. After correction for known risk factors sdc1 >120 ng/mL was independently associated with mortality after 6 months. In our study, sdc1 is independently associated with six-month-mortality after STEMI. Combining clinical evaluation and different biomarkers assessing both infarct-related myocardial injury and systemic stress response might improve the accuracy of predicting clinical prognosis in STEMI patients.
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Affiliation(s)
- Bernhard Wernly
- Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University, Salzburg, Austria
| | - Georg Fuernau
- University Heart Center Lübeck, Medical Clinic II, University Hospital Schleswig-Holstein and German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany
| | - Maryna Masyuk
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany
| | - Johanna Maria Muessig
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany
| | - Susanne Pfeiler
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany
| | - Raphael Romano Bruno
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany
| | - Steffen Desch
- Department of Internal Medicine/Cardiology, Heart Center Leipzig at University of Leipzig and Leipzig Heart Institute, Leipzig, Germany
| | - Phillip Muench
- Department of Internal Medicine/Cardiology, Heart Center Leipzig at University of Leipzig and Leipzig Heart Institute, Leipzig, Germany
| | - Michael Lichtenauer
- Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University, Salzburg, Austria
| | - Malte Kelm
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany
| | - Volker Adams
- Laboratory of Molecular and Experimental Cardiology, Heart Centre Dresden, TU Dresden, Dresden, Germany
| | - Holger Thiele
- Department of Internal Medicine/Cardiology, Heart Center Leipzig at University of Leipzig and Leipzig Heart Institute, Leipzig, Germany
| | - Ingo Eitel
- University Heart Center Lübeck, Medical Clinic II, University Hospital Schleswig-Holstein and German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany
| | - Christian Jung
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany.
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Prognostic Value of MicroRNAs in Patients after Myocardial Infarction: A Substudy of PRAGUE-18. DISEASE MARKERS 2019; 2019:2925019. [PMID: 31781298 PMCID: PMC6875251 DOI: 10.1155/2019/2925019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 08/15/2019] [Accepted: 09/05/2019] [Indexed: 02/02/2023]
Abstract
Background The evaluation of the long-term risk of major adverse cardiovascular events and cardiac death in patients after acute myocardial infarction (AMI) is an established clinical process. Laboratory markers may significantly help with the risk stratification of these patients. Our objective was to find the relation of selected microRNAs to the standard markers of AMI and determine if these microRNAs can be used to identify patients at increased risk. Methods Selected microRNAs (miR-1, miR-133a, and miR-499) were measured in a cohort of 122 patients from the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI treated with primary percutaneous coronary intervention (pPCI)). The cohort was split into two subgroups: 116 patients who did not die (survivors) and 6 patients who died (nonsurvivors) during the 365-day period after AMI. Plasma levels of selected circulating miRNAs were then assessed in combination with high-sensitivity cardiac troponin T (hsTnT) and N-terminal probrain natriuretic peptide (NT-proBNP). Results miR-1, miR-133a, and miR-499 correlated positively with NT-proBNP and hsTnT 24 hours after admission and negatively with left ventricular ejection fraction (LVEF). Both miR-1 and miR-133a positively correlated with hsTnT at admission. Median relative levels of all selected miRNAs were higher in the subgroup of nonsurvivors (N = 6) in comparison with survivors (N = 116), but the difference did not reach statistical significance. All patients in the nonsurvivor subgroup had miR-499 and NT-proBNP levels above the cut-off values (891.5 ng/L for NT-proBNP and 0.088 for miR-499), whereas in the survivor subgroup, only 28.4% of patients were above the cut-off values (p = 0.001). Conclusions Statistically significant correlation was found between miR-1, miR-133a, and miR-499 and hsTnT, NT-proBNP, and LVEF. In addition, this analysis suggests that plasma levels of circulating miR-499 could contribute to the identification of patients at increased risk of death during the first year after AMI, especially when combined with NT-proBNP levels.
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Li Z, Zhang Y, Ding N, Zhao Y, Ye Z, Shen L, Yi H, Zhu Y. Inhibition of lncRNA XIST Improves Myocardial I/R Injury by Targeting miR-133a through Inhibition of Autophagy and Regulation of SOCS2. MOLECULAR THERAPY. NUCLEIC ACIDS 2019; 18:764-773. [PMID: 31734557 PMCID: PMC6861669 DOI: 10.1016/j.omtn.2019.10.004] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 09/26/2019] [Accepted: 10/04/2019] [Indexed: 12/14/2022]
Abstract
The objective of this study was to investigate the role of lncRNA XIST and its relationship with miR-133a in myocardial I/R injury. H9C2 cells treated by hypoxia/reoxygenation (H/R) were used to establish an in vitro I/R model. The small interfering RNA (siRNA) for XIST and miR-133 mimics, inhibitor, and suppressor of cytokine signaling (SOCS2) recombinant plasmids were used to transfect the cells. Cell apoptosis was determined by flow cytometry analysis, and cell viability was used for 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assay. The dual-luciferase reporter assay was performed to confirm binding between XIST and miR-133a, as well as miR-133a and SOCS2. To inhibit or overexpress XIST, miR-133a, or SOCS2 in I/R mice, we used recombinant lentivirus vectors and adenovirus vectors for tail vein injection. The expression of XIST, miR-133a, and SOCS2 was determined by quantitative real-time PCR, and LC3 I/II and Beclin1 was determined by western blotting. The expression of XIST and SOCS2 was significantly upregulated, whereas the miR-133a level was remarkably downregulated in both H/R H9C2 cells and I/R mice myocardial tissues. In both H/R H9C2 cells and I/R mice, the inhibition of XIST led to decreased apoptosis and autophagy, and inhibition of miR-133a reversed these effects. Similarly, overexpression of miR-133a resulted in reduced apoptosis and autophagy, which were reversed by overexpression of SOCS2. The inhibition of XIST and overexpression of miR-133a also promote cell viability of H/R cells. The dual-luciferase reporter assay significantly showed that XIST directly targeted on miR-133a, and miR-133a directly targeted on SOCS2. The inhibition of XIST could improve myocardial I/R injury by regulation of the miR-133a/SOCS2 axis and inhibition of autophagy.
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Affiliation(s)
- Zhiqiang Li
- Department of Cardiovascular Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Yaping Zhang
- Department of Heart Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Nan Ding
- Department of Cardiovascular Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Yudong Zhao
- Department of Cardiovascular Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Zankai Ye
- Department of Cardiovascular Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Lei Shen
- Department of Cardiovascular Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Hanlu Yi
- Department of Cardiovascular Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Yaobin Zhu
- Department of Cardiovascular Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
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Soler-Botija C, Gálvez-Montón C, Bayés-Genís A. Epigenetic Biomarkers in Cardiovascular Diseases. Front Genet 2019; 10:950. [PMID: 31649728 PMCID: PMC6795132 DOI: 10.3389/fgene.2019.00950] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 09/05/2019] [Indexed: 12/16/2022] Open
Abstract
Cardiovascular diseases are the number one cause of death worldwide and greatly impact quality of life and medical costs. Enormous effort has been made in research to obtain new tools for efficient and quick diagnosis and predicting the prognosis of these diseases. Discoveries of epigenetic mechanisms have related several pathologies, including cardiovascular diseases, to epigenetic dysregulation. This has implications on disease progression and is the basis for new preventive strategies. Advances in methodology and big data analysis have identified novel mechanisms and targets involved in numerous diseases, allowing more individualized epigenetic maps for personalized diagnosis and treatment. This paves the way for what is called pharmacoepigenetics, which predicts the drug response and develops a tailored therapy based on differences in the epigenetic basis of each patient. Similarly, epigenetic biomarkers have emerged as a promising instrument for the consistent diagnosis and prognosis of cardiovascular diseases. Their good accessibility and feasible methods of detection make them suitable for use in clinical practice. However, multicenter studies with a large sample population are required to determine with certainty which epigenetic biomarkers are reliable for clinical routine. Therefore, this review focuses on current discoveries regarding epigenetic biomarkers and its controversy aiming to improve the diagnosis, prognosis, and therapy in cardiovascular patients.
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Affiliation(s)
- Carolina Soler-Botija
- Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
| | - Carolina Gálvez-Montón
- Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
| | - Antoni Bayés-Genís
- Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
- Cardiology Service, HUGTiP, Badalona, Spain
- Department of Medicine, Barcelona Autonomous University (UAB), Badalona, Spain
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Li Y, Huo C, Pan T, Li L, Jin X, Lin X, Chen J, Zhang J, Guo Z, Xu J, Li X. Systematic review regulatory principles of non-coding RNAs in cardiovascular diseases. Brief Bioinform 2019; 20:66-76. [PMID: 28968629 DOI: 10.1093/bib/bbx095] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Indexed: 12/31/2022] Open
Abstract
Cardiovascular diseases (CVDs) continue to be a major cause of morbidity and mortality, and non-coding RNAs (ncRNAs) play critical roles in CVDs. With the recent emergence of high-throughput technologies, including small RNA sequencing, investigations of CVDs have been transformed from candidate-based studies into genome-wide undertakings, and a number of ncRNAs in CVDs were discovered in various studies. A comprehensive review of these ncRNAs would be highly valuable for researchers to get a complete picture of the ncRNAs in CVD. To address these knowledge gaps and clinical needs, in this review, we first discussed dysregulated ncRNAs and their critical roles in cardiovascular development and related diseases. Moreover, we reviewed >28 561 published papers and documented the ncRNA-CVD association benchmarking data sets to summarize the principles of ncRNA regulation in CVDs. This data set included 13 249 curated relationships between 9503 ncRNAs and 139 CVDs in 12 species. Based on this comprehensive resource, we summarized the regulatory principles of dysregulated ncRNAs in CVDs, including the complex associations between ncRNA and CVDs, tissue specificity and ncRNA synergistic regulation. The highlighted principles are that CVD microRNAs (miRNAs) are highly expressed in heart tissue and that they play central roles in miRNA-miRNA functional synergistic network. In addition, CVD-related miRNAs are close to one another in the functional network, indicating the modular characteristic features of CVD miRNAs. We believe that the regulatory principles summarized here will further contribute to our understanding of ncRNA function and dysregulation mechanisms in CVDs.
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Affiliation(s)
- Yongsheng Li
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Caiqin Huo
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Tao Pan
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Lili Li
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Xiyun Jin
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Xiaoyu Lin
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Juan Chen
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Jinwen Zhang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Zheng Guo
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Juan Xu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.,Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Ministry of Education, China
| | - Xia Li
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.,Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Ministry of Education, China
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Lin X, Zhang S, Huo Z. Serum Circulating miR-150 is a Predictor of Post-Acute Myocardial Infarction Heart Failure. Int Heart J 2019; 60:280-286. [DOI: 10.1536/ihj.18-306] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Xiaoping Lin
- Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine
| | - Sichen Zhang
- National Center of Gerontology, Beijing Hospital
| | - Zhaoxia Huo
- Experimental Teaching Center, School of Basic Medical Sciences, Zhejiang University
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Wang SR, Chen X, Ling S, Ni RZ, Guo H, Xu JW. MicroRNA expression, targeting, release dynamics and early-warning biomarkers in acute cardiotoxicity induced by triptolide in rats. Biomed Pharmacother 2019; 111:1467-1477. [PMID: 30841462 DOI: 10.1016/j.biopha.2018.12.109] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 12/13/2018] [Accepted: 12/23/2018] [Indexed: 12/21/2022] Open
Abstract
Tripterygium wilfordii Hook. F. is a plant used in traditional Chinese medicine to treat rheumatoid arthritis, lupus erythematosus, and psoriasis in China. However, its main active substance, triptolide, has toxic effects on the heart, liver, and kidneys, which limit its clinical application. Therefore, determining the mechanism of cardiotoxicity in triptolide and identifying effective early-warning biomarkers is beneficial for preventing irreversible myocardial injury. We observed changes in microRNAs and aryl hydrocarbon receptor (AhR) as potential biomarkers in triptolide-induced acute cardiotoxicity by using techniques such as polymerase chain reaction (PCR) assay. The results revealed that triptolide increased the heart/body ratio and caused myocardial fiber breakage, cardiomyocyte hypertrophy, increased cell gaps, and nuclear dissolution in treated male rats. Real-time PCR array detection revealed a more than 2-fold increase in the expression of 108 microRNA genes in the hearts of the male rats; this not only regulated the signaling pathways of ErbB, FOXO, AMPK, Hippo, HIF-1α, mTOR, and PI3K-Akt but also participated in biological processes such as cell adhesion, cell cycling, action potential, locomotory behavior, apoptosis, and DNA binding. Moreover, triptolide reduced the circulatory and cardiac levels of AhR protein as a target of these microRNAs and the messenger RNA expression of its downstream gene CYP1 A1. However, decreases in myocardial lactate dehydrogenase, creatine kinase MB, catalase, and glutathione peroxidase activity and an increase in circulating cardiac troponin I were observed only in male rats. Moreover, plasma microRNAs exhibited dynamic change. These results revealed that circulating microRNAs and AhR protein are potentially early-warning biomarkers for triptolide-induced cardiotoxicity.
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Affiliation(s)
- Shu-Rong Wang
- Epigenetics Laboratory, Institute of Interdisciplinary Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiaomiao Chen
- Epigenetics Laboratory, Institute of Interdisciplinary Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Shuang Ling
- Epigenetics Laboratory, Institute of Interdisciplinary Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Rong-Zhen Ni
- Epigenetics Laboratory, Institute of Interdisciplinary Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Huining Guo
- Epigenetics Laboratory, Institute of Interdisciplinary Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Jin-Wen Xu
- Epigenetics Laboratory, Institute of Interdisciplinary Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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Kumari R, Kumar S, Kant R. Role of circulating miRNAs in the pathophysiology of CVD: As a potential biomarker. GENE REPORTS 2018. [DOI: 10.1016/j.genrep.2018.10.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Ahmed FW, Bakhashab S, Bastaman IT, Crossland RE, Glanville M, Weaver JU. Anti-Angiogenic miR-222, miR-195, and miR-21a Plasma Levels in T1DM Are Improved by Metformin Therapy, Thus Elucidating Its Cardioprotective Effect: The MERIT Study. Int J Mol Sci 2018; 19:ijms19103242. [PMID: 30347712 PMCID: PMC6214022 DOI: 10.3390/ijms19103242] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 09/04/2018] [Accepted: 09/06/2018] [Indexed: 02/07/2023] Open
Abstract
Type 1 diabetes (T1DM) is associated with increased cardiovascular disease (CVD) and reduced life expectancy. We thus hypothesized that anti-angiogenic miRs are increased in T1DM, and the cardioprotective effect of metformin is mediated via reducing those miRs. In an open label, case-controlled study, 23 T1DM patients without CVD were treated with metformin for eight weeks (TG), matched with nine T1DM patients on standard treatment (SG) and 23 controls (CG). Plasma miR-222, miR-195, miR-21a and miR-126 were assayed by real-time RT-qPCR. The results were correlated with: endothelial function (RHI), circulating endothelial progenitor cells (cEPCs) (vascular repair marker, CD45dimCD34+VEGFR2+ cells) and circulating endothelial cells (cECs) (vascular injury marker, CD45dimCD34+CD133-CD144+ cells). miR-222, miR-195 and miR-21a were higher in T1DM than CG; p = 0.009, p < 0.0001, p = 0.0001, respectively. There was an inverse correlation between logmiR-222 and logRHI (p < 0.05) and a direct correlation between logmiR-222 and logCD34+ (p < 0.05) in TG. Metformin reduced miR-222, miR-195 and miR-21a levels in TG; p = 0.007, p = 0.002 p = 0.0012, respectively. miRs remained unchanged in SG. miR-126 was similar in all groups. There was a positive association between changes in logmiR-222 and logcECs after metformin in TG (p < 0.05). Anti-angiogenic miRs are increased in T1DM. Metformin has cardioprotective effects through downregulating miR-222, miR-195 and miR-21a, beyond improving glycemic control.
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Affiliation(s)
- Fahad W Ahmed
- Department of Diabetes, Queen Elizabeth Hospital, Gateshead, Newcastle Upon Tyne NE9 6SH, UK.
- Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK.
- Department of Diabetes and Endocrinology, Royal Sussex County Hospital, Brighton BN2 5BE, UK.
| | - Sherin Bakhashab
- Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK.
- Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah P.O. Box 80218, Saudi Arabia.
- Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah P.O. Box 80216, Saudi Arabia.
| | - Inda T Bastaman
- Department of Diabetes, Queen Elizabeth Hospital, Gateshead, Newcastle Upon Tyne NE9 6SH, UK.
- Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK.
- Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.
| | - Rachel E Crossland
- Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK.
| | - Michael Glanville
- Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK.
| | - Jolanta U Weaver
- Department of Diabetes, Queen Elizabeth Hospital, Gateshead, Newcastle Upon Tyne NE9 6SH, UK.
- Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK.
- Cardiovascular Research Centre, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK.
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40
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Wang C, Jing Q. Non-coding RNAs as biomarkers for acute myocardial infarction. Acta Pharmacol Sin 2018; 39:1110-1119. [PMID: 29698386 DOI: 10.1038/aps.2017.205] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 12/25/2017] [Indexed: 12/13/2022]
Abstract
Acute myocardial infarction (AMI) is a main threat to human lives worldwide. Early and accurate diagnoses warrant immediate medical care, which would reduce mortality and improve prognoses. Circulating non-coding RNAs have been demonstrated to serve as competent biomarkers for various diseases. Following the identification of cardiac-specific microRNA miR-208a in circulation, more non-coding RNAs (miR-1, miR-499 and miR-133) have been identified as biomarkers not only for the diagnosis of AMI but also for prognosis post infarction. Here, we summarized recent findings on non-coding RNAs as biomarkers for early diagnosis of ST-segment elevation myocardial infarction and for disease monitoring of myocardial infarction. In addition, the prognostic potential of non-coding RNAs in patients treated with percutaneous coronary intervention was also described. We also include studies based on biobanks, and build a miRNA release spectrum after AMI, which provides quantitative and time-lapse monitoring of AMI progress. With this spectrum, we are able to customize personal medical care, which prevents further damage. By constructing a network of circulating non-coding RNAs with high specificity and sensitivity, detailed diagnostic information was provided for personalized medicine. Unveiling the roles and kinetics of circulating non-coding RNAs may lead to a revolution in clinical diagnosis.
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Kim JS, Pak K, Goh TS, Jeong DC, Han ME, Kim J, Oh SO, Kim CD, Kim YH. Prognostic Value of MicroRNAs in Coronary Artery Diseases: A Meta-Analysis. Yonsei Med J 2018; 59:495-500. [PMID: 29749132 PMCID: PMC5949291 DOI: 10.3349/ymj.2018.59.4.495] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 03/12/2018] [Accepted: 03/14/2018] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Coronary artery diseases (CADs) are the leading causes of death in the world. Recent studies have reported that differentially expressed microRNAs (miRNAs) are associated with prognosis or major adverse cardiac events (MACEs) in CAD patients. In a previous meta-analysis, the authors made serious mistakes that we aimed to correct through an updated systematic review and meta-analysis of the prognostic value of altered miRNAs in patients with CADs. MATERIALS AND METHODS We performed a systematic search of MEDLINE (from inception to May 2017) and EMBASE (from inception to May 2017) for English-language publications. Studies of CADs with results on miRNAs that reported survival data or MACEs were included. Data were extracted from each publication independently by two reviewers. RESULTS After reviewing 515 articles, a total eight studies were included in this study. We measured pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miRNA 133a with a fixed-effect model (pooled HR, 2.35; 95% CI, 1.56-3.55). High expression of miRNA 133a, 208b, 126, 197, 223, and 122-5p were associated with high mortality. Additionally, high levels of miRNA 208b, 499-5p, 134, 328, and 34a were related with MACEs. CONCLUSION The present study confirmed that miRNA 133a, which was associated with high mortality in CAD patients, holds prognostic value in CAD. More importantly, this study corrected issues raised against a prior meta-analysis and provides accurate information.
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Affiliation(s)
- Ji Suk Kim
- BEER, Busan Society of Evidence-based Mdicine and Research, Busan, Korea
- Department of Family Medicine, BHS Han Seo Hospital, Busan, Korea
| | - Kyoungjune Pak
- BEER, Busan Society of Evidence-based Mdicine and Research, Busan, Korea
- Department of Nuclear Medicine, Pusan National University Hospital, Busan, Korea
| | - Tae Sik Goh
- BEER, Busan Society of Evidence-based Mdicine and Research, Busan, Korea
- Department of Orthopaedic Surgery, Pusan National University Hospital, Busan, Korea
| | | | - Myoung Eun Han
- Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Korea
| | - Jihyun Kim
- Department of Family Medicine, BHS Han Seo Hospital, Busan, Korea
| | - Sae Ock Oh
- Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Korea
| | - Chi Dae Kim
- Department of Pharmacology, School of Medicine, Pusan National University, Yangsan, Korea
| | - Yun Hak Kim
- BEER, Busan Society of Evidence-based Mdicine and Research, Busan, Korea
- Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Korea.
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Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting mRNAs for degradation or translational repression. MiRNAs can be expressed tissue specifically and are altered in response to various physiological conditions. It has recently been shown that miRNAs are released into the circulation, potentially for the purpose of communicating with distant tissues. This manuscript discusses miRNA alterations in cardiac muscle and the circulation during heart failure, a prevalent and costly public health issue. A potential mechanism for how skeletal muscle maladaptations during heart failure could be mediated by myocardium-derived miRNAs released to the circulation is presented. An overview of miRNA alterations in skeletal muscle during the ubiquitous process of aging and perspectives on miRNA interactions during heart failure are also provided.
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Affiliation(s)
- Kevin A Murach
- Center for Muscle Biology, University of Kentucky, Lexington, KY, 40536, USA
- Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, KY, 40536, USA
| | - John J McCarthy
- Center for Muscle Biology, University of Kentucky, Lexington, KY, 40536, USA.
- Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA.
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Koroleva IA, Nazarenko MS, Kucher AN. Role of microRNA in Development of Instability of Atherosclerotic Plaques. BIOCHEMISTRY (MOSCOW) 2018; 82:1380-1390. [PMID: 29223165 DOI: 10.1134/s0006297917110165] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
MicroRNAs are small noncoding single-stranded RNAs that regulate gene expression. Today, we see an increasing number of studies highlighting the important role of microRNAs in the development and progression of cardiovascular diseases caused by atherosclerotic lesions of arteries. We review the available scientific data on association of the expression of these biomolecules with instability of atherosclerotic plaques in animal models and humans. We made special emphasis on miR-21, -100, -127, -133, -143/145, -221/222, and -494 because they were analyzed in more than one study. We discuss the possibility of microRNAs using in the diagnosis and therapy of atherosclerosis and its complications.
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Affiliation(s)
- I A Koroleva
- Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634050, Russia.
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Duan L, Liu C, Hu J, Liu Y, Wang J, Chen G, Li Z, Chen H. Epigenetic mechanisms in coronary artery disease: The current state and prospects. Trends Cardiovasc Med 2017; 28:311-319. [PMID: 29366539 DOI: 10.1016/j.tcm.2017.12.012] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Revised: 12/18/2017] [Accepted: 12/23/2017] [Indexed: 12/12/2022]
Abstract
Coronary artery disease (CAD) is the leading cause of morbidity and mortality. CAD has both genetic and environmental causes. In the past two decades, the understanding of epigenetics has advanced swiftly and vigorously. It has been demonstrated that epigenetic modifications are associated with the onset and progression of CAD. This review aims to improve the understanding of the epigenetic mechanisms closely related to CAD and to provide a novel perspective on the onset and development of CAD. Epigenetic changes include DNA methylation, histone modification, microRNA and lncRNA, which are interrelated with critical genes and influence the expression of those genes. In addition, miRNA plays a diverse role in the pathological process of CAD. Numerous studies have found that some cardiac-specific miRNAs have potential as certain diagnostic biomarkers and treatment targets for CAD. In this review, the aberrant epigenetic mechanisms that contribute to CAD will be discussed. We will also provide novel insight into the epigenetic mechanisms that target CAD.
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Affiliation(s)
- Lian Duan
- Department of Cardiology, Guang' an men Hospital, No. 5 Beixiange, Xicheng District, Beijing, China; Beijing University of Traditional Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, China
| | - Chao Liu
- Department of Cardiology, Guang' an men Hospital, No. 5 Beixiange, Xicheng District, Beijing, China; Beijing University of Traditional Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, China
| | - Junyuan Hu
- Department of Cardiology, Guang' an men Hospital, No. 5 Beixiange, Xicheng District, Beijing, China; Beijing University of Traditional Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, China
| | - Yongmei Liu
- Department of Cardiology, Guang' an men Hospital, No. 5 Beixiange, Xicheng District, Beijing, China
| | - Jie Wang
- Department of Cardiology, Guang' an men Hospital, No. 5 Beixiange, Xicheng District, Beijing, China.
| | - Guang Chen
- Department of Cardiology, Guang' an men Hospital, No. 5 Beixiange, Xicheng District, Beijing, China; Beijing University of Traditional Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, China
| | - Zhaoling Li
- Department of Cardiology, Guang' an men Hospital, No. 5 Beixiange, Xicheng District, Beijing, China
| | - Hengwen Chen
- Department of Cardiology, Guang' an men Hospital, No. 5 Beixiange, Xicheng District, Beijing, China
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de Gonzalo-Calvo D, Iglesias-Gutiérrez E, Llorente-Cortés V. Biomarcadores epigenéticos y enfermedad cardiovascular: los microARN circulantes. Rev Esp Cardiol 2017. [DOI: 10.1016/j.recesp.2017.02.027] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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46
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Keller T, Boeckel JN, Groß S, Klotsche J, Palapies L, Leistner D, Pieper L, Stalla GK, Lehnert H, Silber S, Pittrow D, Maerz W, Dörr M, Wittchen HU, Baumeister SE, Völker U, Felix SB, Dimmeler S, Zeiher AM. Improved risk stratification in prevention by use of a panel of selected circulating microRNAs. Sci Rep 2017; 7:4511. [PMID: 28674420 PMCID: PMC5495799 DOI: 10.1038/s41598-017-04040-w] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 05/08/2017] [Indexed: 01/08/2023] Open
Abstract
Risk stratification is crucial in prevention. Circulating microRNAs have been proposed as biomarkers in cardiovascular disease. Here a miR panel consisting of miRs related to different cardiovascular pathophysiologies, was evaluated to predict outcome in the context of prevention. MiR-34a, miR-223, miR-378, miR-499 and miR-133 were determined from peripheral blood by qPCR and combined to a risk panel. As derivation cohort, 178 individuals of the DETECT study, and as validation cohort, 129 individuals of the SHIP study were used in a case-control approach. Overall mortality and cardiovascular events were outcome measures. The Framingham Risk Score(FRS) and the SCORE system were applied as risk classification systems. The identified miR panel was significantly associated with mortality given by a hazard ratio(HR) of 3.0 (95% (CI): 1.09–8.43; p = 0.034) and of 2.9 (95% CI: 1.32–6.33; p = 0.008) after adjusting for the FRS in the derivation cohort. In a validation cohort the miR-panel had a HR of 1.31 (95% CI: 1.03–1.66; p = 0.03) and of 1.29 (95% CI: 1.02–1.64; p = 0.03) in a FRS/SCORE adjusted-model. A FRS/SCORE risk model was significantly improved to predict mortality by the miR panel with continuous net reclassification index of 0.42/0.49 (p = 0.014/0.005). The present miR panel of 5 circulating miRs is able to improve risk stratification in prevention with respect to mortality beyond the FRS or SCORE.
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Affiliation(s)
- Till Keller
- Department of Internal Medicine III, Cardiology, University Hospital, Goethe University Frankfurt, Frankfurt, Germany. .,German Centre for Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt, Germany. .,Department of Cardiology, Kerckhoff Heart and Thorax Centre, Bad Nauheim, Germany.
| | - Jes-Niels Boeckel
- Department of Internal Medicine III, Cardiology, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.,German Centre for Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt, Germany.,Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany
| | - Stefan Groß
- German Centre for Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt, Germany.,German Centre for Cardiovascular Research (DZHK), Partner site Greifswald, Germany
| | - Jens Klotsche
- Institute of Clinical Psychology and Psychotherapy, Technical University Dresden, Dresden, Germany
| | - Lars Palapies
- Department of Internal Medicine III, Cardiology, University Hospital, Goethe University Frankfurt, Frankfurt, Germany
| | - David Leistner
- Department of Internal Medicine III, Cardiology, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.,German Centre for Cardiovascular Research (DZHK), Partner site Berlin, Germany
| | - Lars Pieper
- Institute of Clinical Psychology and Psychotherapy, Technical University Dresden, Dresden, Germany
| | - Günnter K Stalla
- Max Planck Institute of Psychiatry, Endocrinology, Munich, Munich, Germany
| | | | | | - David Pittrow
- Institute of Clinical Pharmacology, Technical University Dresden, Dresden, Germany
| | - Winfried Maerz
- Synlab Akademie für ärztliche Fortbildung, Synlab Services GmbH, Mannheim, Germany
| | - Marcus Dörr
- Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.,German Centre for Cardiovascular Research (DZHK), Partner site Greifswald, Germany
| | - Hans-Ulrich Wittchen
- Institute of Clinical Psychology and Psychotherapy, Technical University Dresden, Dresden, Germany
| | - Sebastian E Baumeister
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.,Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
| | - Uwe Völker
- Interfaculty Institute for Genetics and Functional Genomics, Department of Cardiology, University Medicine Greifswald, Greifswald, Germany.,German Centre for Cardiovascular Research (DZHK), Partner site Greifswald, Germany
| | - Stephan B Felix
- Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.,German Centre for Cardiovascular Research (DZHK), Partner site Greifswald, Germany
| | - Stefanie Dimmeler
- German Centre for Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt, Germany.,Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany
| | - Andreas M Zeiher
- Department of Internal Medicine III, Cardiology, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.,German Centre for Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt, Germany
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De Rosa R, De Rosa S, Leistner D, Boeckel JN, Keller T, Fichtlscherer S, Dimmeler S, Zeiher AM. Transcoronary Concentration Gradient of microRNA-133a and Outcome in Patients With Coronary Artery Disease. Am J Cardiol 2017; 120:15-24. [PMID: 28511772 DOI: 10.1016/j.amjcard.2017.03.264] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 03/27/2017] [Accepted: 03/27/2017] [Indexed: 12/17/2022]
Abstract
Circulating levels of microRNA (miR)-133a are increased in patients with coronary atherosclerotic disease (CAD). Whether the cardiac release of this miR provides any prognostic information in patients with CAD is currently unknown. We aimed to investigate if changes in concentration of miR-133a trough the coronary circulation may be associated with patients' cardiovascular outcome. We enrolled 111 patients (82 with stable CAD and 29 with acute coronary syndromes [ACS]) who underwent coronary angiography. Circulating levels of miR-133a were measured across the transcoronary circulation. Major adverse cardiac events (MACE: death, nonfatal myocardial infarction, and need for revascularization) were recorded through a median follow-up of 32 months. An increased transcoronary concentration gradient of miR133a showed a significant association with overall rate of MACE at follow-up in patients with both stable CAD and ACS (p = 0.011 and p = 0.002, respectively). At the single end point-analysis, increased transcoronary concentration gradients of miR133a were significantly associated with increased rate of death in patients with ACS (p = 0.017) and with increased incidence of new revascularization because of in-stent restenosis in patients with stable CAD (p = 0.026). Kaplan-Meier curves showed a significantly worse event-free survival in patients with greater transcoronary gradients of miR133a (p = 0.026 in stable CAD group and p = 0.007 for ACS group). Nevertheless, these findings lost their significance after adjustment for common cardiovascular risk factor and high-sensitivity troponin-T. In conclusions, the release of miR133a, as measured by its transcoronary concentration gradient, is associated with a higher incidence of MACE in patients with CAD, but it does not add significant prognostic information compared with traditional prognostic biomarkers, therefore limiting its potential usefulness in the clinical practice. Nevertheless, the differential modulation of miR-133a release in the coronary circulation may reflect pathophysiological mechanism involved in CAD progression and complications and suggest a novel potential role for this miR in the development of in-stent restenosis.
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48
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Šatrauskienė A, Navickas R, Laucevičius A, Huber HJ. Identifying differential miR and gene consensus patterns in peripheral blood of patients with cardiovascular diseases from literature data. BMC Cardiovasc Disord 2017; 17:173. [PMID: 28666417 PMCID: PMC5493858 DOI: 10.1186/s12872-017-0609-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 06/22/2017] [Indexed: 01/13/2023] Open
Abstract
Background Numerous recent studies suggest the potential of circulating MicroRNAs (miRs) in peripheral blood samples as diagnostic or prognostic markers for coronary artery disease (CAD), acute coronary syndrome (ACS) and heart failure (HF). However, literature often remains inconclusive regarding as to which markers are most indicative for which of the above diseases. This shortcoming is mainly due to the lack of a systematic analyses and absence of information on the functional pathophysiological role of these miRs and their target genes. Methods We here provide an-easy-to-use scoring approach to investigate the likelihood of regulation of several miRs and their target genes from literature by identifying consensus patterns of regulation. We therefore have screened over 1000 articles that study mRNA markers in cardiovascular and metabolic diseases, and devised a scoring algorithm to identify consensus means for miRs and genes regulation across several studies. We then aimed to identify differential markers between CAD, ACS and HF. Results We first identified miRs (miR-122, −126, −223, −138 and −370) as commonly regulated within a group of metabolic disease, while investigating cardiac-related pathologies (CAD, ACS, HF) revealed a decisive role of miR-1, −499, −208b, and -133a. Looking at differential markers between cardiovascular disease revealed miR-1, miR-208a and miR-133a to distinguish ACS and CAD to HF. Relating differentially expressed miRs to their putative gene targets using MirTarBase, we further identified HCN2/4 and LASP1 as potential markers of CAD and ACS, but not in HF. Likewise, BLC-2 was found oppositely regulated between CAD and HF. Interestingly, while studying overlap in target genes between CAD, ACS and HF only revealed little similarities, mapping these genes to gene ontology terms revealed a surprising similarity between CAD and ACS compared to HF. Conclusion We conclude that our analysis using gene and miR scores allows the extraction of meaningful markers and the elucidation of differential pathological functions between cardiac diseases and provides a novel approach for literature screening for miR and gene consensus patterns. The analysis is easy to use and extendable upon further emergent literature as we provide an Excel sheet for this analysis to the community. Electronic supplementary material The online version of this article (doi:10.1186/s12872-017-0609-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Agnė Šatrauskienė
- Vilnius University, Faculty of Medicine, Vilnius, Lithuania.,Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania
| | - Rokas Navickas
- Vilnius University, Faculty of Medicine, Vilnius, Lithuania.,Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania
| | - Aleksandras Laucevičius
- Vilnius University, Faculty of Medicine, Vilnius, Lithuania.,Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania
| | - Heinrich J Huber
- Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. .,Institute for Automation Engineering (IFAT), Laboratory for Systems Theory and Automatic Control, Otto-von-Guericke University Magdeburg, 39106, Magdeburg, Germany.
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de Gonzalo-Calvo D, Iglesias-Gutiérrez E, Llorente-Cortés V. Epigenetic Biomarkers and Cardiovascular Disease: Circulating MicroRNAs. ACTA ACUST UNITED AC 2017. [PMID: 28623159 DOI: 10.1016/j.rec.2017.05.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
MicroRNAs (miRNAs) are a class of small noncoding RNA (20-25 nucleotides) involved in gene regulation. In recent years, miRNAs have emerged as a key epigenetic mechanism in the development and physiology of the cardiovascular system. These molecular species regulate basic functions in virtually all cell types, and are therefore directly associated with the pathophysiology of a large number of cardiovascular diseases. Since their relatively recent discovery in extracellular fluids, miRNAs have been studied as potential biomarkers of disease. A wide array of studies have proposed miRNAs as circulating biomarkers of different cardiovascular pathologies (eg, myocardial infarction, coronary heart disease, and heart failure, among others), which may have superior physicochemical and biochemical properties than the conventional protein indicators currently used in clinical practice. In the present review, we provide a brief introduction to the field of miRNAs, paying special attention to their potential clinical application. This includes their possible role as new diagnostic or prognostic biomarkers in cardiovascular disease.
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Affiliation(s)
- David de Gonzalo-Calvo
- Grupo de Lípidos y Patología Cardiovascular, Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
| | | | - Vicenta Llorente-Cortés
- Grupo de Lípidos y Patología Cardiovascular, Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Biomédicas de Barcelona (IibB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain
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50
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Choong OK, Lee DS, Chen CY, Hsieh PCH. The roles of non-coding RNAs in cardiac regenerative medicine. Noncoding RNA Res 2017; 2:100-110. [PMID: 30159427 PMCID: PMC6096405 DOI: 10.1016/j.ncrna.2017.06.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 06/03/2017] [Accepted: 06/05/2017] [Indexed: 02/06/2023] Open
Abstract
The emergence of non-coding RNAs (ncRNAs) has challenged the central dogma of molecular biology that dictates that the decryption of genetic information starts from transcription of DNA to RNA, with subsequent translation into a protein. Large numbers of ncRNAs with biological significance have now been identified, suggesting that ncRNAs are important in their own right and their roles extend far beyond what was originally envisaged. ncRNAs do not only regulate gene expression, but are also involved in chromatin architecture and structural conformation. Several studies have pointed out that ncRNAs participate in heart disease; however, the functions of ncRNAs still remain unclear. ncRNAs are involved in cellular fate, differentiation, proliferation and tissue regeneration, hinting at their potential therapeutic applications. Here, we review the current understanding of both the biological functions and molecular mechanisms of ncRNAs in heart disease and describe some of the ncRNAs that have potential heart regeneration effects.
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Affiliation(s)
- Oi Kuan Choong
- Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.,Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Desy S Lee
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Chen-Yun Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Patrick C H Hsieh
- Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.,Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.,Institute of Medical Genomics and Proteomics, Institute of Clinical Medicine and Department of Surgery, National Taiwan University & Hospital, Taipei 100, Taiwan
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