MicroRNA-24 Regulates Vascularity After Myocardial Infarction
Jan Fiedler,Virginija Jazbutyte,Bettina C. Kirchmaier,Bettina C. Kirchmaier,Shashi Kumar Gupta,Johan M. Lorenzen,Dorothee Hartmann,Paolo Galuppo,Susanne Kneitz,John Pena,Cherin Sohn-Lee,Xavier Loyer,Juergen Soutschek,Thomas Brand,Thomas Brand,Thomas Tuschl,Joerg Heineke,Ulrich Martin,Stefan Schulte-Merker,Georg Ertl,Stefan Engelhardt,Johann Bauersachs,Thomas Thum +22 more
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TLDR
It is shown that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia, and is suitable for therapeutic intervention in the setting of ischemic heart disease.Abstract:
Background—Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood. Methods and Results—Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2–associated death promoter) and Sirtuin...read more
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Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches
TL;DR: This review guides the reader through important aspects of non-coding RNA biology, including their biogenesis, mode of actions, physiological function, as well as their role in the disease context (such as in cancer or the cardiovascular system).
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Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish
Fatma O. Kok,Masahiro Shin,Chih-Wen Ni,Ankit Gupta,Ann S. Grosse,Andreas van Impel,Bettina C. Kirchmaier,Josi Peterson-Maduro,George Kourkoulis,Ira Male,Dana F. DeSantis,Sarah Sheppard-Tindell,Lwaki Ebarasi,Lwaki Ebarasi,Christer Betsholtz,Christer Betsholtz,Stefan Schulte-Merker,Scot A. Wolfe,Nathan D. Lawson +18 more
TL;DR: It is suggested that mutant phenotypes become the standard metric to define gene function in zebrafish, after which Morpholinos that recapitulate respective phenotypes could be reliably applied for ancillary analyses.
Journal ArticleDOI
MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles
Eva van Rooij,Eric N. Olson +1 more
TL;DR: The pharmacokinetic and pharmacodynamic properties of current antimiR designs and their relevance to cardiovascular indications are focused on, and the opportunities and obstacles associated with this new therapeutic modality are evaluated.
Journal ArticleDOI
Prospective study on circulating MicroRNAs and risk of myocardial infarction
Anna Zampetaki,Peter Willeit,Lindsey Tilling,Ignat Drozdov,Marianna Prokopi,Jean-Marie Renard,Jean-Marie Renard,Agnes Mayr,Siegfried Weger,Georg Schett,Ajay M. Shah,Chantal M. Boulanger,Chantal M. Boulanger,Johann Willeit,Philip Chowienczyk,Stefan Kiechl,Manuel Mayr +16 more
TL;DR: In subjects with subsequent myocardial infarction, differential co-expression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature.
Journal ArticleDOI
Animal Models of Heart Failure A Scientific Statement From the American Heart Association
Steven R. Houser,Kenneth B. Margulies,Anne M. Murphy,Francis G. Spinale,Gary S. Francis,Sumanth D. Prabhu,Howard A. Rockman,David A. Kass,Jeffery D. Molkentin,Mark A. Sussman,Walter J. Koch +10 more
TL;DR: The distinctive clinical features of the major causes of HF in humans are defined and those distinctive pathological features ofHF in humans that should be present in an animal model being used to identify fundamental causes ofHF or to test preventative or reparative therapies that could reduce HF morbidity and mortality are recommended.
References
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The functions of animal microRNAs
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Journal ArticleDOI
Silencing of microRNAs in vivo with ‘antagomirs’
Jan Krützfeldt,Nikolaus Rajewsky,Ravi Braich,Kallanthottathil G. Rajeev,Thomas Tuschl,Muthiah Manoharan,Markus Stoffel +6 more
TL;DR: It is shown that a novel class of chemically engineered oligonucleotides, termed ‘antagomirs’, are efficient and specific silencers of endogenous miRNA levels in mice and may represent a therapeutic strategy for silencing miRNAs in disease.
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TL;DR: A relatively small set of miRNAs, many of which are ubiquitously expressed, account for most of the differences in miRNA profiles between cell lineages and tissues.
Journal ArticleDOI
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thomas Thum,Carina Gross,Jan Fiedler,Thomas Fischer,Stephan Kissler,Markus Bussen,Paolo Galuppo,Steffen Just,Wolfgang Rottbauer,Stefan Frantz,Mirco Castoldi,Jürgen Soutschek,Victor Koteliansky,Andreas Rosenwald,M. Albert Basson,Jonathan D. Licht,John T. R. Pena,Sara H. Rouhanifard,Martina U. Muckenthaler,Thomas Tuschl,Gail R. Martin,Johann Bauersachs,Stefan Engelhardt,Stefan Engelhardt +23 more
TL;DR: It is shown that microRNA-21 regulates the ERK–MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function and confirms miR-21 as a disease target in heart failure and establishes the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.
Journal ArticleDOI
MicroRNA-133 controls cardiac hypertrophy
Alessandra Carè,Daniele Catalucci,Federica Felicetti,Désirée Bonci,Antonio Addario,Paolo Gallo,Marie Louise Bang,Patrizia Segnalini,Yusu Gu,Nancy D. Dalton,Leonardo Elia,Michael V.G. Latronico,Morten A. Høydal,Camillo Autore,Matteo Antonio Russo,Gerald W. Dorn,Øyvind Ellingsen,Pilar Ruiz-Lozano,Kirk L. Peterson,Carlo M. Croce,Cesare Peschle,Gianluigi Condorelli +21 more
TL;DR: The data show thatmiR-133, and possibly miR-1, are key regulators of cardiac hypertrophy, suggesting their therapeutic application in heart disease.
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