Noncoding RNAs and myocardial fibrosis

Cardiac stress leads to remodelling of cardiac tissue, which often progresses to heart failure and death. Part of the remodelling process is the formation of fibrotic tissue, which is caused by exaggerated activity of cardiac fibroblasts leading to excessive extracellular matrix production within the myocardium. Noncoding RNAs (ncRNAs) are a diverse group of endogenous RNA-based molecules, which include short (∼22 nucleotides) microRNAs and long ncRNAs (of >200 nucleotides). These ncRNAs can regulate important functions in many cardiovascular cells types. This Review focuses on the role of ncRNAs in cardiac fibrosis; specifically, ncRNAs as therapeutic targets, factors for direct fibroblast transdifferentation, their use as diagnostic and prognostic markers, and their potential to function as paracrine modulators of cardiac fibrosis and remodelling.

[1]  李永军,et al.  Atrial Fibrillation , 1999 .

[2]  A. Haverich,et al.  Cellular dedifferentiation of endothelium is linked to activation and silencing of certain nuclear transcription factors: implications for endothelial dysfunction and vascular biology , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[3]  M. Jessup,et al.  Heart failure. , 2003, The New England journal of medicine.

[4]  Paul Martin,et al.  Wound healing and inflammation genes revealed by array analysis of 'macrophageless' PU.1 null mice , 2004, Genome Biology.

[5]  Xiaoxia Qi,et al.  Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA , 2007, Science.

[6]  C. Croce,et al.  MicroRNA-133 controls cardiac hypertrophy , 2007, Nature Medicine.

[7]  Juan Pablo Couso,et al.  Peptides Encoded by Short ORFs Control Development and Define a New Eukaryotic Gene Family , 2007, PLoS biology.

[8]  Xueli Yuan,et al.  Endothelial-to-mesenchymal transition contributes to cardiac fibrosis , 2007, Nature Medicine.

[9]  Y. Pinto,et al.  Conditional Dicer Gene Deletion in the Postnatal Myocardium Provokes Spontaneous Cardiac Remodeling , 2008, Circulation.

[10]  W. Rottbauer,et al.  MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts , 2008, Nature.

[11]  Jeffrey E. Thatcher,et al.  Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis , 2008, Proceedings of the National Academy of Sciences.

[12]  G. Nuovo,et al.  MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. , 2009, Cardiovascular research.

[13]  R. Duisters,et al.  MIRNA-133 AND MIRNA-30 REGULATE CONNECTIVE TISSUE GROWTH FACTOR: IMPLICATIONS FOR A ROLE OF MIRNAS IN MYOCARDIAL MATRIX REMODELING , 2013 .

[14]  Ning Wang,et al.  Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines. , 2009, Cardiovascular research.

[15]  R. Goldschmeding,et al.  Connective tissue growth factor and cardiac fibrosis , 2009, Acta physiologica.

[16]  S. Kauppinen,et al.  Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. , 2010, The Journal of clinical investigation.

[17]  Michael S. Ewer,et al.  Cardiotoxicity of anticancer treatments: what the cardiologist needs to know , 2010, Nature Reviews Cardiology.

[18]  J. Nerbonne,et al.  MicroRNA-133a Protects Against Myocardial Fibrosis and Modulates Electrical Repolarization Without Affecting Hypertrophy in Pressure-Overloaded Adult Hearts , 2010, Circulation research.

[19]  Takeshi Kimura,et al.  Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway , 2010, Cardiovascular research.

[20]  T. Thum,et al.  Circulating MicroRNAs as Biomarkers and Potential Paracrine Mediators of Cardiovascular Disease , 2010, Circulation. Cardiovascular genetics.

[21]  G. Condorelli,et al.  MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling , 2010, Nature Cell Biology.

[22]  N. Kaminski,et al.  miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis , 2010 .

[23]  M. Vinciguerra,et al.  MicroRNA-29 in Aortic Dilation: Implications for Aneurysm Formation , 2011, Circulation research.

[24]  P. Fawcett,et al.  Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. , 2011, American journal of respiratory cell and molecular biology.

[25]  G. Angelini,et al.  Transplantation of Human Pericyte Progenitor Cells Improves the Repair of Infarcted Heart Through Activation of an Angiogenic Program Involving Micro-RNA-132 , 2011, Circulation research.

[26]  P. Linsley,et al.  Comparison of different miR-21 inhibitor chemistries in a cardiac disease model. , 2011, The Journal of clinical investigation.

[27]  J. Bauersachs,et al.  Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome. , 2011, Journal of molecular and cellular cardiology.

[28]  B. Schroen,et al.  MicroRNA-18 and microRNA-19 regulate CTGF and TSP-1 expression in age-related heart failure , 2011, Aging cell.

[29]  D. Bernstein,et al.  Dynamic microRNA expression during the transition from right ventricular hypertrophy to failure. , 2012, Physiological genomics.

[30]  Haifeng Jin,et al.  Let-7 g is involved in doxorubicin induced myocardial injury. , 2012, Environmental toxicology and pharmacology.

[31]  S. Kauppinen,et al.  Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function , 2012, Proceedings of the National Academy of Sciences.

[32]  Yanjie Lu,et al.  A novel reciprocal loop between microRNA-21 and TGFβRIII is involved in cardiac fibrosis. , 2012, The international journal of biochemistry & cell biology.

[33]  Stephane Heymans,et al.  MicroRNA Profiling Identifies MicroRNA-155 as an Adverse Mediator of Cardiac Injury and Dysfunction During Acute Viral Myocarditis , 2012, Circulation research.

[34]  Aaron N. Chang,et al.  MicroRNA-21 Promotes Fibrosis of the Kidney by Silencing Metabolic Pathways , 2012, Science Translational Medicine.

[35]  Xiaoxia Qi,et al.  Heart repair by reprogramming non-myocytes with cardiac transcription factors , 2012, Nature.

[36]  T. Moccetti,et al.  Role of Mitogen-Activated Protein Kinases in Myocardial Ischemia-Reperfusion Injury during Heart Transplantation , 2012, Journal of transplantation.

[37]  S. Themistoclakis,et al.  Fragmented and delayed electrograms within fibrofatty scar predict arrhythmic events in arrhythmogenic right ventricular cardiomyopathy: results from a prospective risk stratification study. , 2012, Heart rhythm.

[38]  T. Thum MicroRNA therapeutics in cardiovascular medicine , 2012, EMBO molecular medicine.

[39]  Achilleas S. Frangakis,et al.  Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs , 2012, Nature Cell Biology.

[40]  E. Finch,et al.  MicroRNA-Mediated In Vitro and In Vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes , 2012, Circulation research.

[41]  A. Ghosh,et al.  Molecular basis of cardiac endothelial-to-mesenchymal transition (EndMT): differential expression of microRNAs during EndMT. , 2012, Cellular signalling.

[42]  E. Olson,et al.  MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca²⁺ overload and cell death. , 2012, The Journal of clinical investigation.

[43]  U. Laufs,et al.  Role of miR-21 in the pathogenesis of atrial fibrosis , 2012, Basic Research in Cardiology.

[44]  Nadav S. Bar,et al.  Landscape of transcription in human cells , 2012, Nature.

[45]  David Milan,et al.  Inefficient Reprogramming of Fibroblasts into Cardiomyocytes Using Gata4, Mef2c, and Tbx5 , 2012, Circulation research.

[46]  T. Jensen,et al.  Adeno‐associated virus‐delivered polycistronic microRNA‐clusters for knockdown of vascular endothelial growth factor in vivo , 2012, The journal of gene medicine.

[47]  Gianpaolo Zerbini,et al.  MiR‐133a regulates collagen 1A1: Potential role of miR‐133a in myocardial fibrosis in angiotensin II‐dependent hypertension , 2012, Journal of cellular physiology.

[48]  Yingwang,et al.  MicroRNA-101 Inhibited Postinfarct Cardiac Fibrosis and Improved Left Ventricular Compliance via the FBJ Osteosarcoma Oncogene/Transforming Growth Factor-β1 Pathway , 2012 .

[49]  Xiaobin Luo,et al.  Role for MicroRNA-21 in Atrial Profibrillatory Fibrotic Remodeling Associated With Experimental Postinfarction Heart Failure , 2012, Circulation. Arrhythmia and electrophysiology.

[50]  G. Lip,et al.  Atrial fibrillation , 2012, The Lancet.

[51]  Li Qian,et al.  In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes , 2011, Nature.

[52]  Thomas Thum,et al.  MicroRNA-22 increases senescence and activates cardiac fibroblasts in the aging heart , 2012, AGE.

[53]  Howard Y. Chang,et al.  Genome regulation by long noncoding RNAs. , 2012, Annual review of biochemistry.

[54]  M. Goumans,et al.  The arterial and cardiac epicardium in development, disease and repair. , 2012, Differentiation; research in biological diversity.

[55]  T. Thum,et al.  Transforming Growth Factor-&bgr;–Induced Endothelial-to-Mesenchymal Transition Is Partly Mediated by MicroRNA-21 , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[56]  R. Hajjar,et al.  SERCA2a gene therapy restores microRNA-1 expression in heart failure via an Akt/FoxO3A-dependent pathway , 2012, European heart journal.

[57]  S. Nattel,et al.  MicroRNA29: A Mechanistic Contributor and Potential Biomarker in Atrial Fibrillation , 2013, Circulation.

[58]  Da-Zhi Wang,et al.  MicroRNA-22 Regulates Cardiac Hypertrophy and Remodeling in Response to Stress , 2013, Circulation research.

[59]  Howard Y. Chang,et al.  Long Noncoding RNAs: Cellular Address Codes in Development and Disease , 2013, Cell.

[60]  M. Giacca,et al.  Macrophage MicroRNA-155 Promotes Cardiac Hypertrophy and Failure , 2013, Circulation.

[61]  M. Hurlé,et al.  Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients. , 2013, International journal of cardiology.

[62]  A. Jevnikar,et al.  MicroRNA and mRNA Signatures in Ischemia Reperfusion Injury in Heart Transplantation , 2013, PloS one.

[63]  J Michael DiMaio,et al.  Making steady progress on direct cardiac reprogramming toward clinical application. , 2013, Circulation research.

[64]  T. Thum,et al.  Detection and transport mechanisms of circulating microRNAs in neurological, cardiac and kidney diseases. , 2013, Current medicinal chemistry.

[65]  I. Karakikes,et al.  Therapeutic Cardiac‐Targeted Delivery of miR‐1 Reverses Pressure Overload–Induced Cardiac Hypertrophy and Attenuates Pathological Remodeling , 2013, Journal of the American Heart Association.

[66]  R. Kalluri,et al.  miR-21 Promotes Fibrogenic Epithelial-to-Mesenchymal Transition of Epicardial Mesothelial Cells Involving Programmed Cell Death 4 and Sprouty-1 , 2013, PloS one.

[67]  B. Maron,et al.  Hypertrophic cardiomyopathy , 2013, The Lancet.

[68]  Yi Zhang,et al.  Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits , 2013, Cell.

[69]  A. Didangelos,et al.  Extracellular Matrix Secretion by Cardiac Fibroblasts: Role of MicroRNA-29b and MicroRNA-30c , 2013, Circulation research.

[70]  H. Hermeking,et al.  MicroRNA-34a regulates cardiac ageing and function , 2013, Nature.

[71]  Shengshou Hu,et al.  Circulating miRNAs reflect early myocardial injury and recovery after heart transplantation , 2013, Journal of Cardiothoracic Surgery.

[72]  S. Miyagawa,et al.  Impact of microRNA Expression in Human Atrial Tissue in Patients with Atrial Fibrillation Undergoing Cardiac Surgery , 2013, PloS one.

[73]  D. Catalucci,et al.  NF‐κB mediated miR‐26a regulation in cardiac fibrosis , 2013, Journal of cellular physiology.

[74]  Shinsuke Yuasa,et al.  Induction of human cardiomyocyte-like cells from fibroblasts by defined factors , 2013, Proceedings of the National Academy of Sciences.

[75]  R. Shiekhattar,et al.  Long Noncoding RNAs Usher In a New Era in the Biology of Enhancers , 2013, Cell.

[76]  Shi-long Zhong,et al.  Smad3 Inactivation and MiR-29b Upregulation Mediate the Effect of Carvedilol on Attenuating the Acute Myocardium Infarction-Induced Myocardial Fibrosis in Rat , 2013, PloS one.

[77]  G. Paolisso,et al.  Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non‐responders , 2013, European journal of heart failure.

[78]  J. D’hooge,et al.  Long‐Term miR‐669a Therapy Alleviates Chronic Dilated Cardiomyopathy in Dystrophic Mice , 2013, Journal of the American Heart Association.

[79]  R. Geffers,et al.  MicroRNA-Mediated Epigenetic Silencing of Sirtuin1 Contributes to Impaired Angiogenic Responses , 2013, Circulation research.

[80]  E. van Rooij,et al.  Inhibition of MicroRNA-92a Protects Against Ischemia/Reperfusion Injury in a Large-Animal Model , 2013, Circulation.

[81]  T. Thum,et al.  Regulation of cardiac and renal ischemia-reperfusion injury by microRNAs. , 2013, Free radical biology & medicine.

[82]  V. Regitz-Zagrosek,et al.  Sex- and estrogen-dependent regulation of a miRNA network in the healthy and hypertrophied heart. , 2013, International journal of cardiology.

[83]  Thomas Thum,et al.  Non-coding RNAs in cardiac remodeling and heart failure. , 2013, Circulation research.

[84]  P. Couttet,et al.  Heart Structure-Specific Transcriptomic Atlas Reveals Conserved microRNA-mRNA Interactions , 2013, PloS one.

[85]  G. Ewald,et al.  Deep RNA Sequencing Reveals Dynamic Regulation of Myocardial Noncoding RNAs in Failing Human Heart and Remodeling With Mechanical Circulatory Support , 2014, Circulation.

[86]  D. Brenner,et al.  Resident fibroblast lineages mediate pressure overload-induced cardiac fibrosis. , 2014, The Journal of clinical investigation.

[87]  T. Fernandes,et al.  Expression of MicroRNA-29 and Collagen in Cardiac Muscle after Swimming Training in Myocardial-Infarcted Rats , 2014, Cellular Physiology and Biochemistry.

[88]  J. Viereck,et al.  Regulatory RNAs and paracrine networks in the heart. , 2014, Cardiovascular research.

[89]  T. Thum,et al.  microRNA therapeutics in cardiovascular disease models. , 2014, Annual review of pharmacology and toxicology.

[90]  Douglas Losordo,et al.  Exosomes and cardiac repair after myocardial infarction. , 2014, Circulation research.

[91]  S. Nattel,et al.  Atrial remodeling and atrial fibrillation: recent advances and translational perspectives. , 2014, Journal of the American College of Cardiology.

[92]  J. Pepper,et al.  178 Circulating Micrornas for Predicting and Monitoring Response to Mechanical Circulatory Support from a left Ventricular Assist Device , 2014, Heart.

[93]  P. Puthanveetil,et al.  Cardiac miR-133a overexpression prevents early cardiac fibrosis in diabetes , 2014, Journal of cellular and molecular medicine.

[94]  Peter Libby,et al.  Cardiovascular remodelling in coronary artery disease and heart failure , 2014, The Lancet.

[95]  Xiaoke Yin,et al.  Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. , 2014, The Journal of clinical investigation.

[96]  E. Rooij MicroRNA therapeutics for cardiovascular disease , 2014 .

[97]  M. Mayr,et al.  ESC Working Group on Myocardial Function Position Paper: how to study the right ventricle in experimental models , 2014, European journal of heart failure.

[98]  Maria-Teresa Piccoli,et al.  Non-coding RNAs in cardiovascular ageing , 2014, Ageing Research Reviews.

[99]  G. Lemesle,et al.  Circulating Long Noncoding RNA, LIPCAR, Predicts Survival in Patients With Heart Failure , 2014, Circulation research.

[100]  T. Tuschl,et al.  Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers , 2014, Proceedings of the National Academy of Sciences.

[101]  M. Latronico,et al.  Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. , 2014, Journal of the American College of Cardiology.

[102]  T. Engstrøm,et al.  Conditioning techniques and ischemic reperfusion injury in relation to on-pump cardiac surgery , 2014, Scandinavian cardiovascular journal : SCJ.

[103]  S. Dimmeler,et al.  Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth , 2014, Circulation Research.

[104]  F. Liu,et al.  The Long Noncoding RNA CHRF Regulates Cardiac Hypertrophy by Targeting miR-489 , 2014, Circulation research.

[105]  B. Schroen,et al.  microRNA-122 down-regulation may play a role in severe myocardial fibrosis in human aortic stenosis through TGF-β1 up-regulation. , 2014, Clinical science.

[106]  G. Lemesle,et al.  The Circulating Long Non-Coding RNA LIPCAR Predicts Survival in Heart Failure Patients , 2014 .

[107]  Hugo A. Katus,et al.  A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction , 2013, European heart journal.

[108]  R. Guigó,et al.  Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs , 2014, European heart journal.