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
TLDR
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.Abstract:
MicroRNAs comprise a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of microRNAs by several mechanisms has been described in various disease states including cardiac disease. Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21) regulates the ERK-MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function. miR-21 levels are increased selectively in fibroblasts of the failing heart, augmenting ERK-MAP kinase activity through inhibition of sprouty homologue 1 (Spry1). This mechanism regulates fibroblast survival and growth factor secretion, apparently controlling the extent of interstitial fibrosis and cardiac hypertrophy. In vivo silencing of miR-21 by a specific antagomir in a mouse pressure-overload-induced disease model reduces cardiac ERK-MAP kinase activity, inhibits interstitial fibrosis and attenuates cardiac dysfunction. These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts. Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.read more
Citations
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Emerging Evidence of Epigenetic Modifications in Vascular Complication of Diabetes
TL;DR: The role of DNA methylation, modifications of histones and role of non-coding RNAs in vascular complications of diabetes, including cardiomyopathy, nephropathy, and retinopathy is highlighted.
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Circulating biomarkers in pulmonary arterial hypertension: Update and future direction
Beatrice Pezzuto,Roberto Badagliacca,Roberto Poscia,Stefano Ghio,Michele D'Alto,Patrizio Vitulo,Massimilano Mulè,Carlo Albera,Maurizio Volterrani,Francesco Fedele,Carmine Dario Vizza +10 more
TL;DR: An extensive review of circulating biomarkers in PAH is presented and some consideration about potential future direction in this area is presented about research of structural proteins specifically expressed in the pathologic tissue that act as disease-specific markers.
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Deciphering Non-coding RNAs in Cardiovascular Health and Disease.
TL;DR: Important basic and clinical breakthroughs that support employing ncRNAs for treatment or early diagnosis of a variety of CVDs are highlighted, and the most relevant limitations that challenge this novel therapeutic approach are depicted.
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The Impact of Air Pollution on Our Epigenome: How Far Is the Evidence? (A Systematic Review)
Rossella Alfano,Zdenko Herceg,Tim S. Nawrot,Tim S. Nawrot,Marc Chadeau-Hyam,Akram Ghantous,Michelle Plusquin +6 more
TL;DR: This systematic review evaluated existing evidence linking air pollution exposure in humans to major epigenetic mechanisms: DNA methylation, microRNAs, long noncoding RNAs, and chromatin regulation to demonstrate modest effects of air pollution on the methylome.
Journal ArticleDOI
Downregulation of miR-193b in systemic sclerosis regulates the proliferative vasculopathy by urokinase-type plasminogen activator expression.
Naoki Iwamoto,Serena Vettori,Britta Maurer,Matthias Brock,E. Pachera,Astrid Jüngel,Maurizio Calcagni,Michael L. Whitfield,Jörg H W Distler,Oliver Distler +9 more
TL;DR: The downregulation of miR-193b induces the expression of uPA, which increases the number of vascular smooth muscle cells in an uPAR-independent manner and thereby contributes to the proliferative vasculopathy with intimal hyperplasia characteristic for SSc.
References
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