miRNAs in Myocardial Regeneration

Objectives

We like to translate our initial successful miRNA-based therapeutic strategies in small and large animals into first clinical trials in patients with large myocardial infarctions and heart failure.

  • Successful validation of 3 therapeutic microRNA candidates in mouse models of myocardial infarction
  • Identification of best dosing and application routes of miRNA-therapeutics in large animals.
  • Pharmacologic and toxicological evaluation of miRNA therapeutics according to EMEA guidelines.
  • Translation of at least one to two miRNA-therapeutics into a large animal model (pig) of myocardial infarction (therapeutic trial study)
  • Planning of a first clinical phase trial to test miRNA therapeutics in patients
  • Spin-Off of Cardior Pharmaceuticals GmbH
  • Outlook: Drug Development of further noncoding RNA targets available in our IP-protected target pipeline

Research Focus

The Institute Molecular and Translational Therapeutic Strategies (IMTTS) was founded in 2009 at the Hannover Medical School by Prof. Thomas Thum. A main group’s focus is the development of RNA-based therapeutic strategies in cardiovascular medicine. Currently we particularly focus on the regeneration as well as treatment of injured organs by use of genetic and pharmacological RNA manipulation with a strong focus on noncoding RNAs, such as microRNAs, long-noncoding RNAs and circular RNAs (e.g. Nature, 2008; Nature Comm 2012; Science Transl Med 2016; Circ Res 2017).

The Institute is also interested to develop companion diagnostic approaches in cardiovascular diseased patients and is firmly integrated into European and International Networks. RNA drug development pipelines have been set up including high-throughput technologies such as RNA profiling, functional profiling strategies, indicative tox and PK studies, safety and efficacy studies in small and large animals. IMTTS also works closely together with the Hannover Clinical Research Center (CRC), the Fraunhofer ITEM and many other national and international Universities, biotech companies and larger pharmaceutical industries. A recent spin-off of IMTTS is Cardior Pharmaceuticals GmbH, that had licensed IMTTS technology to develop innovative ncRNA-based treatment strategies and to perform first clinical trials in cardiovascular patients.

Collaborations

  • U. Martin, REBIRTH Unit iPSCs for disease modelling, drug screening and cell therapy: Our miRNA-based therapeutic approaches (antifibrotic, proangiogenic) will likely facilitate therapeutic success of transplantation of cardiovascular stem cells (including iPS cell-derived cardiovascular cells) to the infarcted hearts. 
  • J. Bauersachs, D. Hilfiker-Kleiner, REBIRTH Unit Endogenous Regeneration Mechanisms of the Heart: Myocardial infarction models 
  • M. Elff, N.N., Niedersächsisches Zentrum für Biomedizintechnik (NIFE) 
  • J. Heineke, REBIRTH Unit Myocardial Cellular Crosstalk and Gene-Therapy: Cardiovascular signalling, Cell-Cell communication 
  • Dr. T. Cantz, REBIRTH Unit Translational Hepatology and Stem Cell Biology; Prof. T. Moritz REBIRTH Unit iPSC based Haematopoietic Regeneration: iPS cell reprogramming using miRNAs 
  • A. Bleich, Central Animal Laboratory, MHH: Planning of large animal models
  • P. Zsolt, University of Kaposvar, Hungary; M. Gyongyosi, University of Vienna, Austria: Large animal models of myocardial infarction. 
  • T. Tuschl, Rockefeller University, New York, M. Mayr, London, UK: microRNA target analysis 

Publications

2013 - ongoing

2017

Ishikawa D, Diekmann U, Fiedler J, Just A, Thum T, Lenzen S, Naujok O. miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions. Stem Cell Reports. 2017/11/16 ed2017. p. 1588-603.

Gupta SK, Garg A, Bär C, Chatterjee S, Foinquinos A, Milting H, Streckfuss-Bomeke K, Fiedler J, Thum T. Quaking Inhibits Doxorubicin-Mediated Cardiotoxicity Through Regulation of Cardiac Circular RNA Expression. Circ Res. 2017/11/15 ed2017.

Dubois-Deruy E, Cuvelliez M, Fiedler J, Charrier H, Mulder P, Hebbar E, Pfanne A, Beseme O, Chwastyniak M, Amouyel P, Richard V, Bauters C, Thum T, Pinet F. MicroRNAs regulating superoxide dismutase 2 are new circulating biomarkers of heart failure. Sci Rep. 2017/11/09 ed2017. p. 14747.

Beermann J, Kirste D, Iwanov K, Lu D, Kleemiss F, Kumarswamy R, Schimmel K, Bär C, Thum T. A large shRNA library approach identifies lncRNA Ntep as an essential regulator of cell proliferation. Cell Death Differ. 2017/11/04 ed2017.

Bär C, Thum T. A long way for microRNAs to become meaningful prognostic biomarkers. Eur J Heart Fail. 2017/10/19 ed2017.

Kleeberger JA, Neuser J, de Gonzalo-Calvo D, Kempf T, Bauersachs J, Thum T, Widder JD. microRNA-206 correlates with left ventricular function after transcatheter aortic valve implantation (TAVI). Am J Physiol Heart Circ Physiol. 2017/10/17 ed2017. p. ajpheart 00432 2017.

Masson S, Batkai S, Beermann J, Bär C, Pfanne A, Thum S, Magnoli M, Balconi G, Nicolosi GL, Tavazzi L, Latini R, Thum T. Circulating microRNA-132 levels improve risk prediction for heart failure hospitalization in patients with chronic heart failure. Eur J Heart Fail. 2017/10/14 ed2017.

Gyöngyösi M, Pavo N, Lukovic D, Zlabinger K, Spannbauer A, Traxler D, Goliasch G, Mandic L, Bergler-Klein J, Gugerell A, Jakab A, Szankai Z, Toth L, Garamvölgyi R, Maurer G, Jaisser F, Zannad F, Thum T, Batkai S, Winkler J. Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension. J Transl Med. 2017/10/08 ed2017. p. 202.

Batkai S, Bär C, Thum T. MicroRNAs in right ventricular remodelling. Cardiovasc Res. 2017/09/29 ed2017. p. 1433-40.

Fiedler J, Grönniger E, Pfanne A, Brönneke S, Schmidt K, Falk CS, Wenck H, Terstegen L, Thum T, Winnefeld M. Identification of miR-126 as a new regulator of skin ageing. Exp Dermatol. 2016/08/31 ed2017. p. 284-6.

Verma K, Jyotsana N, Buenting I, Luther S, Pfanne A, Thum T, Ganser A, Heuser M, Weissinger EM, Hambach L. miR-625-3p is upregulated in CD8+ T cells during early immune reconstitution after allogeneic stem cell transplantation. PLoS One. 2017/08/31 ed2017. p. e0183828.

Piccoli MT, Gupta SK, Viereck J, Foinquinos A, Samolovac S, Kramer FL, Garg A, Remke J, Zimmer K, Batkai S, Thum T. Inhibition of the Cardiac Fibroblast-Enriched lncRNA Meg3 Prevents Cardiac Fibrosis and Diastolic Dysfunction. Circ Res. 2017/06/21 ed2017. p. 575-83.

Chatterjee S, Bär C, Thum T. Linc-ing the Noncoding Genome to Heart Function: Beating Hypertrophy. Trends Mol Med. 2017/06/04 ed2017. p. 577-9.

Müller-Deile J, Dannenberg J, Schroder P, Lin MH, Miner JH, Chen R, Brasen JH, Thum T, Nystrom J, Staggs LB, Haller H, Fiedler J, Lorenzen JM, Schiffer M. Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases. Kidney Int. 2017/05/10 ed2017. p. 836-49.

Bär C, Thum T. Changing Direction: From Therapeutic Telomerase Inhibition to Activation? Circ Res. 2017/04/30 ed2017. p. 1393-5.

Schauerte C, Hübner A, Rong S, Wang S, Shushakova N, Mengel M, Dettling A, Bang C, Scherf K, Koelling M, Melk A, Haller H, Thum T, Lorenzen JM. Antagonism of profibrotic microRNA-21 improves outcome of murine chronic renal allograft dysfunction. Kidney Int. 2017/04/12 ed2017. p. 646-56.

Devaux Y, Creemers EE, Boon RA, Werfel S, Thum T, Engelhardt S, Dimmeler S, Squire I, Cardiolinc n. Circular RNAs in heart failure. Eur J Heart Fail. 2017/03/28 ed2017. p. 701-9.

Gupta SK, Thum T. MiR-142-3p is a paracrine mediator between T cells and endothelium during allograft rejection. Cardiovasc Res. 2017/03/25 ed2017. p. 431-3.

Pfaff N, Liebhaber S, Möbus S, Beh-Pajooh A, Fiedler J, Pfanne A, Schambach A, Thum T, Cantz T, Moritz T. Inhibition of miRNA-212/132 improves the reprogramming of fibroblasts into induced pluripotent stem cells by de-repressing important epigenetic remodelling factors. Stem Cell Res. 2017/03/18 ed2017. p. 70-5.

Xiao K, Thum T. Exosomal MicroRNAs Released by Pediatric Cardiac Progenitor Cells. Circ Res. 2017/02/18 ed2017. p. 607-9.

Kölling M, Kaucsar T, Schauerte C, Hubner A, Dettling A, Park JK, Busch M, Wulff X, Meier M, Scherf K, Bukosza N, Szenasi G, Godo M, Sharma A, Heuser M, Hamar P, Bang C, Haller H, Thum T, Lorenzen JM. Therapeutic miR-21 Silencing Ameliorates Diabetic Kidney Disease in Mice. Mol Ther. 2017/01/28 ed2017. p. 165-80.

Viereck J, Thum T. Long Noncoding RNAs in Pathological Cardiac Remodeling. Circulation research. 2017;120(2):262-4.

Viereck J, Thum T. Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury. Circulation research. 2017;120(2):381-99.

Neumann A, Napp LC, Kleeberger JA, Benecke N, Pfanne A, Haverich A, Thum T, Bara C. MicroRNA 628-5p as a Novel Biomarker for Cardiac Allograft Vasculopathy. Transplantation. 2017;101(1):e26-e33.

2016

de Gonzalo-Calvo D, Kenneweg F, Bang C, Toro R, van der Meer RW, Rijzewijk LJ, Smit JWA, Lamb HJ, Llorente-Cortes V, Thum T. Circulating Long Noncoding RNAs in Personalized Medicine: Response to Pioglitazone Therapy in Type 2 Diabetes. Journal of the American College of Cardiology2016. p. 2914-6.

Weber N, Schwanke K, Greten S, Wendland M, Iorga B, Fischer M, Geers-Knorr C, Hegermann J, Wrede C, Fiedler J, Kempf H, Franke A, Piep B, Pfanne A, Thum T, Martin U, Brenner B, Zweigerdt R, Kraft T. Stiff matrix induces switch to pure beta-cardiac myosin heavy chain expression in human ESC-derived cardiomyocytes. Basic research in cardiology. 2016;111(6):68.

Viereck J, Kumarswamy R, Foinquinos A, Xiao K, Avramopoulos P, Kunz M, Dittrich M, Maetzig T, Zimmer K, Remke J, Just A, Fendrich J, Scherf K, Bolesani E, Schambach A, Weidemann F, Zweigerdt R, de Windt LJ, Engelhardt S, Dandekar T, Batkai S, Thum T. Long noncoding RNA Chast promotes cardiac remodeling. Science translational medicine. 2016;8(326):326ra22.

Hartmann D, Fiedler J, Sonnenschein K, Just A, Pfanne A, Zimmer K, Remke J, Foinquinos A, Butzlaff M, Schimmel K, Maegdefessel L, Hilfiker-Kleiner D, Lachmann N, Schober A, Froese N, Heineke J, Bauersachs J, Batkai S, Thum T. MicroRNA-Based Therapy of GATA2-Deficient Vascular Disease. Circulation. 2016;134(24):1973-90.

Gupta SK, Thum T. Non-coding RNAs as orchestrators of autophagic processes. Journal of molecular and cellular cardiology. 2016;95:26-30.

Gupta SK, Foinquinos A, Thum S, Remke J, Zimmer K, Bauters C, de Groote P, Boon RA, de Windt LJ, Preissl S, Hein L, Batkai S, Pinet F, Thum T. Preclinical Development of a MicroRNA-Based Therapy for Elderly Patients With Myocardial Infarction. Journal of the American College of Cardiology. 2016;68(14):1557-71.

Goldschmidt I, Thum T, Baumann U. Circulating miR-21 and miR-29a as Markers of Disease Severity and Etiology in Cholestatic Pediatric Liver Disease. Journal of clinical medicine. 2016;5(3).

Fiedler J, Thum T. New Insights Into miR-17-92 Cluster Regulation and Angiogenesis. Circulation research. 2016;118(1):9-11.

Fiedler J, Gronniger E, Pfanne A, Bronneke S, Schmidt K, Falk CS, Wenck H, Terstegen L, Thum T, Winnefeld M. Identification of miR-126 as a new regulator of skin aging. Experimental dermatology. 2016.

de Gonzalo-Calvo D, Kenneweg F, Bang C, Toro R, van der Meer RW, Rijzewijk LJ, Smit JW, Lamb HJ, Llorente-Cortes V, Thum T. Circulating long-non coding RNAs as biomarkers of left ventricular diastolic function and remodelling in patients with well-controlled type 2 diabetes. Scientific reports. 2016;6:37354.

Daniel JM, Prock A, Dutzmann J, Sonnenschein K, Thum T, Bauersachs J, Sedding DG. Regulator of G-Protein Signaling 5 Prevents Smooth Muscle Cell Proliferation and Attenuates Neointima Formation. Arteriosclerosis, thrombosis, and vascular biology. 2016;36(2):317-27.

Beermann J, Piccoli MT, Viereck J, Thum T. Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. Physiological reviews. 2016;96(4):1297-325.

Bar C, Chatterjee S, Thum T. Long Noncoding RNAs in Cardiovascular Pathology, Diagnosis, and Therapy. Circulation. 2016;134(19):1484-99.

2015

Voigtlander T, Gupta SK, Thum S, Fendrich J, Manns MP, Lankisch TO, Thum T. MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma. PloS one. 2015;10(10):e0139305.

Thum T. Antiageing concepts and cardiovascular disease. European heart journal. 2015;36(48):3435-6.

Sorensen-Zender I, Bhayana S, Susnik N, Rolli V, Batkai S, Baisantry A, Bahram S, Sen P, Teng B, Lindner R, Schiffer M, Thum T, Melk A, Haller H, Schmitt R. Zinc-alpha2-Glycoprotein Exerts Antifibrotic Effects in Kidney and Heart. Journal of the American Society of Nephrology : JASN. 2015;26(11):2659-68.

Piccoli MT, Gupta SK, Thum T. Noncoding RNAs as regulators of cardiomyocyte proliferation and death. Journal of molecular and cellular cardiology. 2015;89(Pt A):59-67.

Lorenzen JM, Schauerte C, Kolling M, Hubner A, Knapp M, Haller H, Thum T. Long Noncoding RNAs in Urine Are Detectable and May Enable Early Detection of Acute T Cell-Mediated Rejection of Renal Allografts. Clinical chemistry. 2015;61(12):1505-14.

Fiedler J, Breckwoldt K, Remmele CW, Hartmann D, Dittrich M, Pfanne A, Just A, Xiao K, Kunz M, Muller T, Hansen A, Geffers R, Dandekar T, Eschenhagen T, Thum T. Development of Long Noncoding RNA-Based Strategies to Modulate Tissue Vascularization. Journal of the American College of Cardiology. 2015;66(18):2005-15.

Bang C, Antoniades C, Antonopoulos AS, Eriksson U, Franssen C, Hamdani N, Lehmann L, Moessinger C, Mongillo M, Muhl L, Speer T, Thum T. Intercellular communication lessons in heart failure. European journal of heart failure. 2015;17(11):1091-103.

Lorenzen JM, Schauerte C, Kielstein JT, Hubner A, Martino F, Fiedler J, Gupta SK, Faulhaber-Walter R, Kumarswamy R, Hafer C, Haller H, Fliser D, Thum T. Circulating Long Noncoding Rnatapsaki Is a Predictor of Mortality in Critically Ill Patients with Acute Kidney Injury. Clin Chem. 2015;61(1):191-201. Epub 2014/10/09.

Mayer SC, Gilsbach R, Preissl S, Monroy Ordonez EB, Schnick T, Beetz N, Lother A, Rommel C, Ihle H, Bugger H, Ruhle F, Schrepper A, Schwarzer M, Heilmann C, Bonisch U, Gupta SK, Wilpert J, Kretz O, von Elverfeldt D, Orth J, Aktories K, Beyersdorf F, Bode C, Stiller B, Kruger M, Thum T, Doenst T, Stoll M, Hein L. Adrenergic Repression of the Epigenetic Reader Mecp2 Facilitates Cardiac Adaptation in Chronic Heart Failure. Circ Res. 2015;117(7):622-33. Epub 2015/07/22.

Varga ZV, Giricz Z, Bencsik P, Madonna R, Gyongyosi M, Schulz R, Mayr M, Thum T, Puskas LG, Ferdinandy P. Functional Genomics of Cardioprotection by Ischemic Conditioning and the Influence of Comorbid Conditions: Implications in Target Identification. Curr Drug Targets. 2015;16(8):904-11. Epub 2015/04/29.

Thum T. Antiageing Concepts and Cardiovascular Disease. Eur Heart J. 2015. Epub 2015/08/22.

Zwadlo C, Schmidtmann E, Szaroszyk M, Kattih B, Froese N, Hinz H, Schmitto JD, Widder J, Batkai S, Bahre H, Kaever V, Thum T, Bauersachs J, Heineke J. Antiandrogenic Therapy with Finasteride Attenuates Cardiac Hypertrophy and Left Ventricular Dysfunction. Circulation. 2015;131(12):1071-81. Epub 2015/01/30.

Bantel H, Thum T, Schulze-Osthoff K. Reply: To Pmid 24913549. Hepatology. 2015;61(4):1440-1.

Derda AA, Thum S, Lorenzen JM, Bavendiek U, Heineke J, Keyser B, Stuhrmann M, Givens RC, Kennel PJ, Schulze PC, Widder JD, Bauersachs J, Thum T. Blood-Based Microrna Signatures Differentiate Various Forms of Cardiac Hypertrophy. Int J Cardiol. 2015;196:115-22. Epub 2015/06/19.

Sorensen-Zender I, Bhayana S, Susnik N, Rolli V, Batkai S, Baisantry A, Bahram S, Sen P, Teng B, Lindner R, Schiffer M, Thum T, Melk A, Haller H, Schmitt R. Zinc-Alpha2-Glycoprotein Exerts Antifibrotic Effects in Kidney and Heart. J Am Soc Nephrol. 2015;26(11):2659-68. Epub 2015/03/20.

Heymans S, Gonzalez A, Pizard A, Papageorgiou AP, Lopez-Andres N, Jaisser F, Thum T, Zannad F, Diez J. Searching for New Mechanisms of Myocardial Fibrosis with Diagnostic and/or Therapeutic Potential. Eur J Heart Fail. 2015;17(8):764-71. Epub 2015/07/02.

Dangwal S, Stratmann B, Bang C, Lorenzen JM, Kumarswamy R, Fiedler J, Falk CS, Scholz CJ, Thum T, Tschoepe D. Impairment of Wound Healing in Patients with Type 2 Diabetes Mellitus Influences Circulating Microrna Patterns Via Inflammatory Cytokines. Arterioscler Thromb Vasc Biol. 2015;35(6):1480-8. Epub 2015/03/31.

Li XG, Roivainen A, Bergman J, Heinonen A, Bengel F, Thum T, Knuuti J. Enabling [(18)F]-Bicyclo[6.1.0]Nonyne for Oligonucleotide Conjugation for Positron Emission Tomography Applications: [(18)F]-Anti-Microrna-21 as an Example. Chem Commun (Camb). 2015;51(48):9821-4. Epub 2015/05/20.

Watson CJ, Gupta SK, O’Connell E, Thum S, Glezeva N, Fendrich J, Gallagher J, Ledwidge M, Grote-Levi L, McDonald K, Thum T. Microrna Signatures Differentiate Preserved from Reduced Ejection Fraction Heart Failure. Eur J Heart Fail. 2015;17(4):405-15. Epub 2015/03/06.

Bang C, Antoniades C, Antonopoulos AS, Eriksson U, Franssen C, Hamdani N, Lehmann L, Moessinger C, Mongillo M, Muhl L, Speer T, Thum T. Intercellular Communication Lessons in Heart Failure. Eur J Heart Fail. 2015. Epub 2015/09/24.

Voigtlander T, Gupta SK, Thum S, Fendrich J, Manns MP, Lankisch TO, Thum T. Micrornas in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma. PLoS One. 2015;10(10):e0139305. Epub 2015/10/03.

Piccoli MT, Gupta SK, Thum T. Noncoding Rnas as Regulators of Cardiomyocyte Proliferation and Death. J Mol Cell Cardiol. 2015. Epub 2015/02/11.

Hirt MN, Werner T, Indenbirken D, Alawi M, Demin P, Kunze AC, Stenzig J, Starbatty J, Hansen A, Fiedler J, Thum T, Eschenhagen T. Deciphering the Microrna Signature of Pathological Cardiac Hypertrophy by Engineered Heart Tissue- and Sequencing-Technology. J Mol Cell Cardiol. 2015;81:1-9. Epub 2015/01/31.

Ahlbrecht J, Martino F, Pul R, Skripuletz T, Suhs KW, Schauerte C, Yildiz O, Trebst C, Tasto L, Thum S, Pfanne A, Roesler R, Lauda F, Hecker M, Zettl UK, Tumani H, Thum T, Stangel M. Deregulation of Microrna-181c in Cerebrospinal Fluid of Patients with Clinically Isolated Syndrome Is Associated with Early Conversion to Relapsing-Remitting Multiple Sclerosis. Mult Scler. 2015. Epub 2015/10/24.

Thum T, Condorelli G. Long Noncoding Rnas and Micrornas in Cardiovascular Pathophysiology. Circ Res. 2015;116(4):751-62. Epub 2015/02/14.

Fiedler J, Breckwoldt K, Remmele CW, Hartmann D, Dittrich M, Pfanne A, Just A, Xiao K, Kunz M, Muller T, Hansen A, Geffers R, Dandekar T, Eschenhagen T, Thum T. Development of Long Noncoding Rna-Based Strategies to Modulate Tissue Vascularization. J Am Coll Cardiol. 2015;66(18):2005-15.

Viereck J, Kumarswamy R, Thum T. Long Noncoding Rnas as Inducers and Terminators of Vascular Development. Circulation. 2015;131(14):1236-8. Epub 2015/03/06.

Devaux Y, Zangrando J, Schroen B, Creemers EE, Pedrazzini T, Chang CP, Dorn GW, 2nd, Thum T, Heymans S. Long Noncoding Rnas in Cardiac Development and Ageing. Nat Rev Cardiol. 2015;12(7):415-25. Epub 2015/04/10.

Lorenzen JM, Schauerte C, Kolling M, Hubner A, Knapp M, Haller H, Thum T. Long Noncoding Rnas in Urine Are Detectable and May Enable Early Detection of Acute T Cell-Mediated Rejection of Renal Allografts. Clin Chem. 2015. Epub 2015/10/29.

Van Aelst LN, Summer G, Li S, Gupta SK, Heggermont W, De Vusser K, Carai P, Naesens M, Van Cleemput J, Van de Werf F, Vanhaecke J, Thum T, Waer M, Papageorgiou AP, Schroen B, Heymans S. Rna Profiling in Human and Murine Transplanted Hearts: Identification and Validation of Therapeutic Targets for Acute Cardiac and Renal Allograft Rejection. Am J Transplant. 2015. Epub 2015/08/08.

Lorenzen JM, Schauerte C, Hubner A, Kolling M, Martino F, Scherf K, Batkai S, Zimmer K, Foinquinos A, Kaucsar T, Fiedler J, Kumarswamy R, Bang C, Hartmann D, Gupta SK, Kielstein J, Jungmann A, Katus HA, Weidemann F, Muller OJ, Haller H, Thum T. Osteopontin Is Indispensible for Ap1-Mediated Angiotensin Ii-Related Mir-21 Transcription During Cardiac Fibrosis. Eur Heart J. 2015;36(32):2184-96. Epub 2015/04/23.

2014

Batkai S, Thum T. Analytical Approaches in Microrna Therapeutics. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;964:146-52.

Kunz M, Xiao K, Liang C, Viereck J, Pachel C, Frantz S, Thum T, Dandekar T. Bioinformatics of Cardiovascular Mirna Biology. J Mol Cell Cardiol. 2014.

Bang C, Batkai S, Dangwal S, Gupta SK, Foinquinos A, Holzmann A, Just A, Remke J, Zimmer K, Zeug A, Ponimaskin E, Schmiedl A, Yin X, Mayr M, Halder R, Fischer A, Engelhardt S, Wei Y, Schober A, Fiedler J, Thum T. Cardiac Fibroblast-Derived Microrna Passenger Strand-Enriched Exosomes Mediate Cardiomyocyte Hypertrophy. J Clin Invest. 2014;124(5):2136-46. Epub 2014/04/20.

Sassi Y, Ahles A, Truong DJ, Baqi Y, Lee SY, Husse B, Hulot JS, Foinquinos A, Thum T, Muller CE, Dendorfer A, Laggerbauer B, Engelhardt S. Cardiac Myocyte-Secreted Camp Exerts Paracrine Action Via Adenosine Receptor Activation. J Clin Invest. 2014;124(12):5385-97.

Kumarswamy R, Bauters C, Volkmann I, Maury F, Fetisch J, Holzmann A, Lemesle G, de Groote P, Pinet F, Thum T. Circulating Long Noncoding Rna, Lipcar, Predicts Survival in Patients with Heart Failure. Circ Res. 2014;114(10):1569-75.

Mooren FC, Viereck J, Kruger K, Thum T. Circulating Micrornas as Potential Biomarkers of Aerobic Exercise Capacity. Am J Physiol Heart Circ Physiol. 2014;306(4):H557-63.

Morley-Smith AC, Mills A, Jacobs S, Meyns B, Rega F, Simon AR, Pepper JR, Lyon AR, Thum T. Circulating Micrornas for Predicting and Monitoring Response to Mechanical Circulatory Support from a Left Ventricular Assist Device. Eur J Heart Fail. 2014;16(8):871-9.

Thum T. Noncoding Rnas and Myocardial Fibrosis. Nat Rev Cardiol. 2014;11(11):655-63.

33.

Thum T, Batkai S. Micrornas in Right Ventricular (Dys)Function (2013 Grover Conference Series). Pulm Circ. 2014;4(2):185-90.

Lorenzen JM, Kaucsar T, Schauerte C, Schmitt R, Rong S, Hubner A, Scherf K, Fiedler J, Martino F, Kumarswamy R, Kolling M, Sorensen I, Hinz H, Heineke J, van Rooij E, Haller H, Thum T. Microrna-24 Antagonism Prevents Renal Ischemia Reperfusion Injury. J Am Soc Nephrol. 2014;25(12):2717-29.

Osipova J, Fischer DC, Dangwal S, Volkmann I, Widera C, Schwarz K, Lorenzen JM, Schreiver C, Jacoby U, Heimhalt M, Thum T, Haffner D. Diabetes-Associated Micrornas in Pediatric Patients with Type 1 Diabetes Mellitus: A Cross-Sectional Cohort Study. J Clin Endocrinol Metab. 2014;99(9):E1661-5.

John K, Hadem J, Krech T, Wahl K, Manns MP, Dooley S, Batkai S, Thum T, Schulze-Osthoff K, Bantel H. Micrornas Play a Role in Spontaneous Recovery from Acute Liver Failure. Hepatology. 2014;60(4):1346-55.

Radke RM, Diller GP, Duck M, Orwat S, Hartmann D, Thum T, Baumgartner H. Endothelial Function in Contemporary Patients with Repaired Coarctation of Aorta. Heart. 2014;100(21):1696-701.

Leite-Moreira AF, Lourenco AP, Balligand JL, Bauersachs J, Clerk A, De Windt LJ, Heymans S, Hilfiker-Kleiner D, Hirsch E, Iaccarino G, Kaminski KA, Knoll R, Mayr M, Tarone G, Thum T, Tocchetti CG. Esc Working Group on Myocardial Function Position Paper: How to Study the Right Ventricle in Experimental Models. European Journal of Heart Failure. 2014;16(5):509-18.

Dangwal S, Thum T. Microrna Therapeutics in Cardiovascular Disease Models. Annu Rev Pharmacol Toxicol. 2014;54:185-203.

Fiedler J, Stohr A, Gupta SK, Hartmann D, Holzmann A, Just A, Hansen A, Hilfiker-Kleiner D, Eschenhagen T, Thum T. Functional Microrna Library Screening Identifies the Hypoxamir Mir-24 as a Potent Regulator of Smooth Muscle Cell Proliferation and Vascularization. Antioxidants & Redox Signaling. 2014;21(8):1167-76.

Hirsch E, Nagai R, Thum T. Heterocellular Signalling and Crosstalk in the Heart in Ischaemia and Heart Failure. Cardiovasc Res. 2014;102(2):191-3.

Winkler C, Bahlmann O, Viereck J, Knudsen L, Wedekind D, Hoymann HG, Madsen J, Thum T, Hohlfeld JM, Ochs M. Impact of a Met(11)Thr Single Nucleotide Polymorphism of Surfactant Protein D on Allergic Airway Inflammation in a Murine Asthma Model. Exp Lung Res. 2014;40(4):154-63.

Blecharz KG, Burek M, Bauersachs J, Thum T, Tsikas D, Widder J, Roewer N, Forster CY. Inhibition of Proteasome-Mediated Glucocorticoid Receptor Degradation Restores Nitric Oxide Bioavailability in Myocardial Endothelial Cells in Vitro. Biol Cell. 2014;106(7):219-35.

Trettin A, Modun D, Madunic S, Vukovic J, Radman M, Batkai S, Thum T, Jordan J, Tsikas D. Lc-Ms/Ms and Gc-Ms/Ms Measurement of Plasma and Urine Di-Paracetamol and 3-Nitro-Paracetamol: Proof-of-Concept Studies on a Novel Human Model of Oxidative Stress Based on Oral Paracetamol Administration. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;959:71-81.

Thum T, Fiedler J. Lincing Malat1 and Angiogenesis. Circ Res. 2014;114(9):1366-8.

Lankisch TO, Voigtlander T, Manns MP, Holzmann A, Dangwal S, Thum T. Micrornas in the Bile of Patients with Biliary Strictures after Liver Transplantation. Liver Transpl. 2014;20(6):673-8.

Thum T. Non-Coding Rnas in Ageing. Ageing Res Rev. 2014;17:1-2.

Fiedler J, Batkai S, Thum T. Microrna-Based Therapy in Cardiology. Herz. 2014;39(2):194-200.

Gupta SK, Piccoli MT, Thum T. Non-Coding Rnas in Cardiovascular Ageing. Ageing Res Rev. 2014;17:79-85.

Rayner K, Dimmeler S, Calin GA, Thum T, Raizman JE, Diamandis EP. Novel Biomarkers for Acute Myocardial Infarction: Is Microrna the New Kid on the Block? Clin Chem. 2014;60(6):812-7.

Springer J, Tschirner A, Haghikia A, von Haehling S, Lal H, Grzesiak A, Kaschina E, Palus S, Potsch M, von Websky K, Hocher B, Latouche C, Jaisser F, Morawietz L, Coats AJ, Beadle J, Argiles JM, Thum T, Foldes G, Doehner W, Hilfiker-Kleiner D, Force T, Anker SD. Prevention of Liver Cancer Cachexia-Induced Cardiac Wasting and Heart Failure. Eur Heart J. 2014;35(14):932-41.

Jaguszewski M, Osipova J, Ghadri JR, Napp LC, Widera C, Franke J, Fijalkowski M, Nowak R, Fijalkowska M, Volkmann I, Katus HA, Wollert KC, Bauersachs J, Erne P, Lscher TF, Thum T, Templin C. A Signature of Circulating Micrornas Differentiates Takotsubo Cardiomyopathy from Acute Myocardial Infarction. European Heart Journal. 2014;35(15):999-+.

Viereck J, Bang C, Foinquinos A, Thum T. Regulatory Rnas and Paracrine Networks in the Heart. Cardiovasc Res. 2014;102(2):290-301.

Varga ZV, Zvara A, Farago N, Kocsis GF, Pipicz M, Gaspar R, Bencsik P, Gorbe A, Csonka C, Puskas LG, Thum T, Csont T, Ferdinandy P. Micrornas Associated with Ischemia-Reperfusion Injury and Cardioprotection by Ischemic Pre- and Postconditioning: Protectomirs. Am J Physiol Heart Circ Physiol. 2014;307(2):H216-27.

Thum T, Kumarswamy R. The Smooth Long Noncoding Rna Sencr. Arterioscler Thromb Vasc Biol. 2014;34(6):1124-5.

Tarone G, Balligand JL, Bauersachs J, Clerk A, De Windt L, Heymans S, Hilfiker-Kleiner D, Hirsch E, Iaccarino G, Knoll R, Leite-Moreira AF, Lourenco AP, Mayr M, Thum T, Tocchetti CG. Targeting Myocardial Remodelling to Develop Novel Therapies for Heart Failure a Position Paper from the Working Group on Myocardial Function of the European Society of Cardiology. European Journal of Heart Failure. 2014;16(5):494-508.

Batkai S, Thum T. Towards Novel Theranostic Approaches in Cardiac Transplantation Medicine. Eur Heart J. 2014;35(45):3152-4.

Trettin A, Batkai S, Thum T, Jordan J, Tsikas D. Trapping of Napqi, the Intermediate Toxic Paracetamol Metabolite, by Aqueous Sulfide (S(2)(-)) and Analysis by Gc-Ms/Ms. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;963:99-105.

Kumarswamy R, Volkmann I, Beermann J, Napp LC, Jabs O, Bhayadia R, Melk A, Ucar A, Chowdhury K, Lorenzen JM, Gupta SK, Batkai S, Thum T. Vascular Importance of the Mir-212/132 Cluster. Eur Heart J. 2014;35(45):3224-31.

2013

Tutarel O, Dangwal S, Bretthauer J, Westhoff-Bleck M, Roentgen P, Anker SD, Bauersachs J, Thum T. Circulating Mir-423_5p Fails as a Biomarker for Systemic Ventricular Function in Adults after Atrial Repair for Transposition of the Great Arteries. Int J Cardiol. 2013;167(1):63-6.

Lorenzen JM, Martino F, Thum T. Detection and Transport Mechanisms of Circulating Micrornas in Neurological, Cardiac and Kidney Diseases. Curr Med Chem. 2013;20(29):3623-8. Epub 2013/07/10.

Kaucsar T, Revesz C, Godo M, Krenacs T, Albert M, Szalay CI, Rosivall L, Benyo Z, Batkai S, Thum T, Szenasi G, Hamar P. Activation of the Mir-17 Family and Mir-21 During Murine Kidney Ischemia-Reperfusion Injury. Nucleic Acid Ther. 2013;23(5):344-54.

Heymans S, Corsten MF, Verhesen W, Carai P, van Leeuwen RE, Custers K, Peters T, Hazebroek M, Stoger L, Wijnands E, Janssen BJ, Creemers EE, Pinto YM, Grimm D, Schurmann N, Vigorito E, Thum T, Stassen F, Yin X, Mayr M, de Windt LJ, Lutgens E, Wouters K, de Winther MP, Zacchigna S, Giacca M, van Bilsen M, Papageorgiou AP, Schroen B. Macrophage Microrna-155 Promotes Cardiac Hypertrophy and Failure. Circulation. 2013;128(13):1420-32.

Volkmann I, Kumarswamy R, Pfaff N, Fiedler J, Dangwal S, Holzmann A, Batkai S, Geffers R, Lother A, Hein L, Thum T. Microrna-Mediated Epigenetic Silencing of Sirtuin1 Contributes to Impaired Angiogenic Responses. Circ Res. 2013;113(8):997-1003.

Lorenzen JM, Dietrich B, Fiedler J, Jazbutyte V, Fleissner F, Karpinski N, Weidemann F, Wanner C, Asan E, Caprio M, Ertl G, Bauersachs J, Thum T. Pathologic Endothelial Response and Impaired Function of Circulating Angiogenic Cells in Patients with Fabry Disease. Basic Res Cardiol. 2013;108(1):311.

Jazbutyte V, Fiedler J, Kneitz S, Galuppo P, Just A, Holzmann A, Bauersachs J, Thum T. Microrna-22 Increases Senescence and Activates Cardiac Fibroblasts in the Aging Heart. Age (Dordr). 2013;35(3):747-62.

Thum T. Microrna-223 Made Its Way into Vascular Research. Circ Res. 2013;113(12):1270-1.

Lorenzen JM, Batkai S, Thum T. Regulation of Cardiac and Renal Ischemia-Reperfusion Injury by Micrornas. Free Radic Biol Med. 2013;64:78-84.

Fiedler J, Thum T. Micrornas in Myocardial Infarction. Arterioscler Thromb Vasc Biol. 2013;33(2):201-5.

Dangwal S, Thum T. Micrornas in Platelet Physiology and Pathology. Hamostaseologie. 2013;33(1):17-20.

Lorenzen JM, Thum T. Micrornas in Idiopathic Childhood Nephrotic Syndrome. Clin Chem. 2013;59(4):595-7.

Kumarswamy R, Thum T. Non-Coding Rnas in Cardiac Remodeling and Heart Failure. Circ Res. 2013;113(6):676-89.

Diekmann U, Elsner M, Fiedler J, Thum T, Lenzen S, Naujok O. Microrna Target Sites as Genetic Tools to Enhance Promoter-Reporter Specificity for the Purification of Pancreatic Progenitor Cells from Differentiated Embryonic Stem Cells. Stem Cell Rev. 2013;9(5):555-68.

Bauters C, Kumarswamy R, Holzmann A, Bretthauer J, Anker SD, Pinet F, Thum T. Circulating Mir-133a and Mir-423-5p Fail as Biomarkers for Left Ventricular Remodeling after Myocardial Infarction. Int J Cardiol. 2013;168(3):1837-40.

Ganesan J, Ramanujam D, Sassi Y, Ahles A, Jentzsch C, Werfel S, Leierseder S, Loyer X, Giacca M, Zentilin L, Thum T, Laggerbauer B, Engelhardt S. Mir-378 Controls Cardiac Hypertrophy by Combined Repression of Mitogen-Activated Protein Kinase Pathway Factors. Circulation. 2013;127(21):2097-106.

Emanueli C, Thum T. Mirnage-34 Induces Cardiac Damage. Cell Res. 2013;23(7):866-7.

Baumgarten A, Bang C, Tschirner A, Engelmann A, Adams V, von Haehling S, Doehner W, Pregla R, Anker MS, Blecharz K, Meyer R, Hetzer R, Anker SD, Thum T, Springer J. Twist1 Regulates the Activity of Ubiquitin Proteasome System Via the Mir-199/214 Cluster in Human End-Stage Dilated Cardiomyopathy. Int J Cardiol. 2013;168(2):1447-52.

Dirkx E, Gladka MM, Philippen LE, Armand AS, Kinet V, Leptidis S, El Azzouzi H, Salic K, Bourajjaj M, da Silva GJ, Olieslagers S, van der Nagel R, de Weger R, Bitsch N, Kisters N, Seyen S, Morikawa Y, Chanoine C, Heymans S, Volders PG, Thum T, Dimmeler S, Cserjesi P, Eschenhagen T, da Costa Martins PA, De Windt LJ. Nfat and Mir-25 Cooperate to Reactivate the Transcription Factor Hand2 in Heart Failure. Nat Cell Biol. 2013;15(11):1282-93.

2006 - 2012

2012

Bang C, Thum T. Exosomes: New Players in Cell-Cell Communication. Int J Biochem Cell Biol. 2012;44(11):2060-4.

Ucar A, Gupta SK, Fiedler J, Erikci E, Kardasinski M, Batkai S, Dangwal S, Kumarswamy R, Bang C, Holzmann A, Remke J, Caprio M, Jentzsch C, Engelhardt S, Geisendorf S, Glas C, Hofmann TG, Nessling M, Richter K, Schiffer M, Carrier L, Napp LC, Bauersachs J, Chowdhury K, Thum T. The Mirna-212/132 Family Regulates Both Cardiac Hypertrophy and Cardiomyocyte Autophagy. Nature Communications. 2012;3.

Dangwal S, Hartmann D, Thum T. Micrornas Deciding Cardiac Stem Cell Fate. J Mol Cell Cardiol. 2012;53(6):747-8.

Pfaff N, Moritz T, Thum T, Cantz T. Mirnas Involved in the Generation, Maintenance, and Differentiation of Pluripotent Cells. Journal of Molecular Medicine. 2012;90(7):747-52.

Kumarswamy R, Lyon AR, Volkmann I, Mills AM, Bretthauer J, Pahuja A, Geers-Knorr C, Kraft T, Hajjar RJ, Macleod KT, Harding SE, Thum T. Serca2a Gene Therapy Restores Microrna-1 Expression in Heart Failure Via an Akt/Foxo3a-Dependent Pathway. Eur Heart J. 2012;33(9):1067-75.

Haghikia A, Haghikia A, Hellwig K, Baraniskin A, Holzmann A, Decard BF, Thum T, Gold R. Regulated Micrornas in the Csf of Patients with Multiple Sclerosis: A Case-Control Study. Neurology. 2012;79(22):2166-70.

2011

Pfaff N, Fiedler J, Holzmann A, Schambach A, Moritz T, Cantz T, Thum T. Mirna Screening Reveals a New Mirna Family Stimulating Ips Cell Generation Via Regulation of Meox2. EMBO Rep. 2011;12(11):1153-9.

Fiedler J, Jazbutyte V, Kirchmaier BC, Gupta SK, Lorenzen J, Hartmann D, Galuppo P, Kneitz S, Pena JTG, Sohn-Lee C, Loyer X, Soutschek J, Brand T, Tuschl T, Heineke J, Martin U, Schulte-Merker S, Ertl G, Engelhardt S, Bauersachs J, Thum T. Microrna-24 Regulates Vascularity after Myocardial Infarction. Circulation. 2011;124(6):720-U178.

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