Secreted factors and non-cell-based strategies for cardiac regeneration

Objectives

Acute myocardial infarction (MI) is the leading cause of heart failure worldwide. In the Division of Molecular and Translational Cardiology we are investigating the mechanisms that promote heart failure development after MI. Our goal is to develop more effective diagnostic and therapeutic strategies to prevent heart failure. Within REBIRTH, we are developing non-invasive strategies to improve wound healing and heart regeneration after MI.

Research Focus

The development of heart failure after MI is determined by the extent of the infarct, the wound healing response, and chronic left ventricular remodelling. The wound healing response provides a largely unexploited therapeutic window of opportunity to improve outcome after MI. Wound healing involves multiple cell types that are interacting with each other in a highly orchestrated manner. This inter-cellular communication occurs primarily through secreted proteins. The importance of paracrine signalling in the infarcted heart suggests that individual secreted proteins might be developed as therapeutic agents (biologics) after MI. Protein based therapeutics have several potential advantages, including ease of standardisation and large-scale production; the potential for off-the-shelf, systemic, and repetitive administration, and the potential to design protein cocktails tailored to specific disease settings. Based on bioinformatic secretome analyses and functional screens, we have recently identified two previously uncharacterised angiogenic proteins, myeloid-derived growth factor (MYDGF) and ER membrane protein complex subunit 10 (EMC10), that promote heart repair after MI. We found that transient systemic application of MYDGF or EMC10 mediate sustained beneficial effects on heart function and survival after MI (Nat Med 2015, Circulation 2017). We have applied for a patent covering the use of these newly identified angiogenic growth factors as a therapy for ischemic tissue repair. In collaboration with an industry partner we are developing these factors towards clinical application.

Collaborations

  • A. Schambach, REBIRTH Unit 6.2 Regenerative Gene Therapy, Experimental Haematology, MHH
  • F. Bengel, REBIRTH Unit 8.3 Radionuclide Molecular Imaging, Dept. of Nuclear Medicine, MHH
  • I. Gruh, REBIRTH Unit 5.7 Myocardial Tissue Engineering, LEBAO, MHH
  • M. Ballmaier, FACS core facility, MHH
  • A. Pich, Core Unit Mass Spectrometry and Proteomics, Institute of Toxicology, MHH

Further Research Projects

  • Role of new secreted factors during cardiac hypertrophy and failure
  • Role of small open reading frame-encoded polypeptides during heart failure and reverse remodelling

Teaching

  • Lecturer in the PhD programme ‚Regenerative Sciences’
  • Multiple roles as Lecturer for Medical students in their 3rd, 4th, 5th, and 6th year at Hannover Medical School

Selected Publications

Reboll MR, Korf-Klingebiel M, Klede S, Polten F, Brinkmann E, Reimann I, Schönfeld H-J, Bobadilla M, Faix J, Kensah G, Gruh I, Klintschar M, Gaestel M, Niessen HW, Pich A, Bauersachs J, Gogos JA, Wang Y, Wollert KC. EMC10 (Endoplasmic Reticulum Membrane Protein Complex Subunit 10) Is a Bone Marrow-Derived Angiogenic Growth Factor Promoting Tissue Repair after Myocardial Infarction. Circulation. 2017;136:1809-23.

Wollert KC, Meyer GP, Müller-Ehmsen J, Tschöpe C, Bonarjee V, Larsen AI, May AE, Empen K, Chorianopoulos E, Tebbe U, Waltenberger J, Mahrholdt H, Ritter B, Pirr J, Fischer D, Korf-Klingebiel M, Arseniev L, Heuft H-G, Brinchmann JE, Messinger D, Hertenstein B, Ganser A, Katus HA, Felix SB, Gawaz MP, Dickstein K, Schultheiss H-P, Ladage D, Greulich S, Bauersachs J. Intracoronary Autologous Bone Marrow Cell Transfer after Myocardial Infarction: The BOOST-2 Randomised Placebo-Controlled Clinical Trial. European Heart Journal. 2017;38:2936-43.

Korf-Klingebiel M, Reboll MR, Klede S, Brod T, Pich A, Polten F, Napp LC, Bauersachs J, Ganser A, Brinkmann E, Reimann I, Kempf T, Niessen HW, Mizrahi J, Schönfeld H-J, Iglesias A, Bobadilla M, Wang Y, Wollert KC. Myeloid-Derived Growth Factor (C19orf10) Mediates Cardiac Repair Following Myocardial Infarction. Nature Medicine. 2015;21:140-9.

Widera C, Pencina MJ, Meisner A, Kempf T, Bethmann K, Marquardt I, Katus HA, Giannitsis E, Wollert KC. Adjustment of the GRACE Score by Growth Differentiation Factor 15 Enables a More Accurate Appreciation of Risk in Non-ST-Elevation Acute Coronary Syndrome. European Heart Journal. 2012;33:1095-104.

Korf-Klingebiel M, Kempf T, Schlüter K-D, Willenbockel C, Brod T, Heineke J, Schmidt VJ, Jantzen F, Brandes RP, Sugden PH, Drexler H, Molkentin JD, Wollert KC. Transgenic Expression of Fibroblast Growth Factor 9 in the Adult Mouse Heart Reduces Heart Failure Mortality after Myocardial Infarction. Circulation. 2011;123:504-14.

Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, Bolomini-Vittori M, Korf-Klingebiel M, Napp LC, Hansen B, Kanwischer A, Bavendiek U, Beutel G, Hapke M, Sauer MG, Laudanna C, Hogg N, Vestweber D, Wollert KC. GDF-15 Is an Inhibitor of Leukocyte Integrin Activation Required for Survival after Myocardial Infarction in Mice. Nature Medicine. 2011;17:581-8.

Bonaca MP, Morrow DA, Braunwald E, Cannon CP, Jiang S, Breher S, Sabatine MS, Kempf T, Wallentin L, Wollert KC. Growth Differentiation Factor-15 and Risk of Recurrent Events in Patients Stabilized after Acute Coronary Syndrome: Observations from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol. 2011;31:203-10.

Anand IS, Kempf T, Rector TS, Tapken H, Allhoff T, Jantzen F, Kuskowski M, Cohn JN, Drexler H, Wollert KC. Serial Measurement of Growth-Differentiation Factor-15 in Heart Failure. Circulation. 2010;122:1387-95.

Wollert KC, Kempf T, Lagerqvist B, Lindahl B, Olofsson S, Allhoff T, Peter T, Siegbahn A, Venge P, Drexler H, Wallentin L. Growth Differentiation Factor 15 for Risk Stratification and Selection of an Invasive Treatment Strategy in Non ST-Elevation Acute Coronary Syndrome. Circulation. 2007;116:1540-8.

Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary Autologous Bone-Marrow Cell Transfer After Myocardial Infarction. The BOOST Randomised Controlled Clinical Trial. Lancet. 2004;364:141-148.

Publications

2013 - ongoing

2017

Reboll MR, Korf-Klingebiel M, Klede S, Polten F, Brinkmann E, Reimann I, Schonfeld HJ, Bobadilla M, Faix J, Kensah G, Gruh I, Klintschar M, Gaestel M, Niessen HW, Pich A, Bauersachs J, Gogos JA, Wang Y, Wollert KC. EMC10 (Endoplasmic Reticulum Membrane Protein Complex Subunit 10) Is a Bone Marrow-Derived Angiogenic Growth Factor Promoting Tissue Repair After Myocardial Infarction. Circulation. 2017/09/22 ed2017. p. 1809-23.

Wollert KC, Meyer GP, Muller-Ehmsen J, Tschope C, Bonarjee V, Larsen AI, May AE, Empen K, Chorianopoulos E, Tebbe U, Waltenberger J, Mahrholdt H, Ritter B, Pirr J, Fischer D, Korf-Klingebiel M, Arseniev L, Heuft HG, Brinchmann JE, Messinger D, Hertenstein B, Ganser A, Katus HA, Felix SB, Gawaz MP, Dickstein K, Schultheiss HP, Ladage D, Greulich S, Bauersachs J. Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial. Eur Heart J. 2017/04/22 ed2017. p. 2936-43.

Malek Mohammadi M, Kattih B, Grund A, Froese N, Korf-Klingebiel M, Gigina A, Schrameck U, Rudat C, Liang Q, Kispert A, Wollert KC, Bauersachs J, Heineke J. The transcription factor GATA4 promotes myocardial regeneration in neonatal mice. EMBO molecular medicine. 2017;9(2):265-79.

Appari M, Breitbart A, Brandes F, Szaroszyk M, Froese N, Korf-Klingebiel M, Mohammadi MM, Grund A, Scharf GM, Wang H, Zwadlo C, Fraccarollo D, Schrameck U, Nemer M, Wong GW, Katus HA, Wollert KC, Muller OJ, Bauersachs J, Heineke J. C1q-TNF-Related Protein-9 Promotes Cardiac Hypertrophy and Failure. Circulation research. 2017;120(1):66-77.

2016

Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction. Theranostics. 2016;6(11):1768-79.

Haddad S, Wang Y, Galy B, Korf-Klingebiel M, Hirsch V, Baru AM, Rostami F, Reboll MR, Heineke J, Flogel U, Groos S, Renner A, Toischer K, Zimmermann F, Engeli S, Jordan J, Bauersachs J, Hentze MW, Wollert KC, Kempf T. Iron-regulatory proteins secure iron availability in cardiomyocytes to prevent heart failure. Eur Heart J. 2016/08/23 ed2017. p. 362-72.

2015

Wollert KC. Ischaemic risk and bleeding risk in acute coronary syndrome: still inseparable. Eur Heart J. 2015; in press (Editorial).

Wollert KC. Bone Marrow Mononuclear Cell Therapy for Acute Myocardial Infarction: We Know What We Want, but We Just Don't Know How Yet. Heart. 2015;101(5):337-8. Epub 2015/01/21.

Thackeray JT, Derlin T, Haghikia A, Napp LC, Wang Y, Ross TL, Schafer A, Tillmanns J, Wester HJ, Wollert KC, Bauersachs J, Bengel FM. Molecular Imaging of the Chemokine Receptor Cxcr4 after Acute Myocardial Infarction. JACC Cardiovasc Imaging. 2015.

Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Clinically Relevant Strategies for Lowering Cardiomyocyte Glucose Uptake for F-18-Fdg Imaging of Myocardial Inflammation in Mice. European Journal of Nuclear Medicine and Molecular Imaging. 2015;42(5):771-80.

Thackeray JT, Bankstahl JP, Wang Y, Korf-Klingebiel M, Walte A, Wittneben A, Wollert KC, Bengel FM. Targeting Post-Infarct Inflammation by Pet Imaging: Comparison of Ga-68-Citrate and Ga-68-Dotatate with F-18-Fdg in a Mouse Model. European Journal of Nuclear Medicine and Molecular Imaging. 2015;42(2):317-27.

Sinning JM, Wollert KC, Sedaghat A, Widera C, Radermacher MC, Descoups C, Hammerstingl C, Weber M, Stundl A, Ghanem A, Widder J, Vasa-Nicotera M, Mellert F, Schiller W, Bauersachs J, Zur B, Holdenrieder S, Welz A, Grube E, Pencina MJ, Nickenig G, Werner N, Kempf T. Risk Scores and Biomarkers for the Prediction of 1-Year Outcome after Transcatheter Aortic Valve Replacement. Am Heart J. 2015;170(4):821-9.

Korf-Klingebiel M, Reboll MR, Klede S, Brod T, Pich A, Polten F, Napp LC, Bauersachs J, Ganser A, Brinkmann E, Reimann I, Kempf T, Niessen HW, Mizrahi J, Schonfeld HJ, Iglesias A, Bobadilla M, Wang Y, Wollert KC. Myeloid-Derived Growth Factor (C19orf10) Mediates Cardiac Repair Following Myocardial Infarction. Nature Medicine. 2015;21(2):52-61.

Andersson C, Preis SR, Beiser A, DeCarli C, Wollert KC, Wang TJ, Januzzi JL, Jr., Vasan RS, Seshadri S. Associations of Circulating Growth Differentiation Factor-15 and St2 Concentrations with Subclinical Vascular Brain Injury and Incident Stroke. Stroke. 2015;46(9):2568-75.

2014

Xanthakis V, Enserro DM, Murabito JM, Polak JF, Wollert KC, Januzzi JL, Wang TJ, Tofler G, Vasan RS. Ideal Cardiovascular Health: Associations with Biomarkers and Subclinical Disease and Impact on Incidence of Cardiovascular Disease in the Framingham Offspring Study. Circulation. 2014;130(19):1676-83.

Gopal DM, Larson MG, Januzzi JL, Cheng S, Ghorbani A, Wollert KC, Kempf T, D'Agostino RB, Polak JF, Ramachandran VS, Wang TJ, Ho JE. Biomarkers of Cardiovascular Stress and Subclinical Atherosclerosis in the Community. Clin Chem. 2014;60(11):1402-8.

Delewi R, Hirsch A, Tijssen JG, Schachinger V, Wojakowski W, Roncalli J, Aakhus S, Erbs S, Assmus B, Tendera M, Turan RG, Corti R, Henry T, Lemarchand P, Lunde K, Cao F, Huikuri HV, Surder D, Simari RD, Janssens S, Wollert KC, Plewka M, Grajek S, Traverse JH, Zijlstra F, Piek JJ. Impact of Intracoronary Bone Marrow Cell Therapy on Left Ventricular Function in the Setting of St-Segment Elevation Myocardial Infarction: A Collaborative Meta-Analysis. European Heart Journal. 2014;35(15):989-98.

Bar C, Bernardes de Jesus B, Serrano R, Tejera A, Ayuso E, Jimenez V, Formentini I, Bobadilla M, Mizrahi J, de Martino A, Gomez G, Pisano D, Mulero F, Wollert KC, Bosch F, Blasco MA. Telomerase Expression Confers Cardioprotection in the Adult Mouse Heart after Acute Myocardial Infarction. Nat Commun. 2014;5:5863.

Kapopara PR, von Felden J, Soehnlein O, Wang Y, Napp LC, Sonnenschein K, Wollert KC, Schieffer B, Gaestel M, Bauersachs J, Bavendiek U. Deficiency of Mapk-Activated Protein Kinase 2 (Mk2) Prevents Adverse Remodelling and Promotes Endothelial Healing after Arterial Injury. Thromb Haemost. 2014;112(6):1264-76.

2013

Widera C, Pencina MJ, Bobadilla M, Reimann I, Guba-Quint A, Marquardt I, Bethmann K, Korf-Klingebiel M, Kempf T, Lichtinghagen R, Katus HA, Giannitsis E, Wollert KC. Incremental Prognostic Value of Biomarkers Beyond the Grace (Global Registry of Acute Coronary Events) Score and High-Sensitivity Cardiac Troponin T in Non-St-Elevation Acute Coronary Syndrome. Clinical Chemistry. 2013;59(10):1497-505.

Breitbart A, Scharf GM, Duncker D, Widera C, Gottlieb J, Vogel A, Schmidt S, Brandes G, Heuft HG, Lichtinghagen R, Kempf T, Wollert KC, Bauersachs J, Heineke J. Highly Specific Detection of Myostatin Prodomain by an Immunoradiometric Sandwich Assay in Serum of Healthy Individuals and Patients. Plos One. 2013;8(11).

Bengel FM, George RT, Schuleri KH, Lardo AC, Wollert KC. Image-Guided Therapies for Myocardial Repair: Concepts and Practical Implementation. European Heart Journal-Cardiovascular Imaging. 2013;14(8):741-51.

2006 - 2012

2012

Widera C, Pencina MJ, Meisner A, Kempf T, Bethmann K, Marquardt I, Katus HA, Giannitsis E, Wollert KC. Adjustment of the Grace Score by Growth Differentiation Factor 15 Enables a More Accurate Appreciation of Risk in Non-St-Elevation Acute Coronary Syndrome. European Heart Journal. 2012;33(9):1095-104.

Widera C, Giannitsis E, Kempf T, Korf-Klingebiel M, Fiedler B, Sharma S, Katus HA, Asaumi Y, Shimano M, Walsh K, Wollert KC. Identification of Follistatin-Like 1 by Expression Cloning as an Activator of the Growth Differentiation Factor 15 Gene and a Prognostic Biomarker in Acute Coronary Syndrome. Clinical Chemistry. 2012;58(8):1233-41.

Wang TJ, Wollert KC, Larson MG, Coglianese E, McCabe EL, Cheng SS, Ho JE, Fradley MG, Ghorbani A, Xanthakis V, Kempf T, Benjamin EJ, Levy D, Vasan RS, Januzzi JL. Prognostic Utility of Novel Biomarkers of Cardiovascular Stress the Framingham Heart Study. Circulation. 2012;126(13):1596-+.

2011

Korf-Klingebiel M, Kempf T, Schluter KD, Willenbockel C, Brod T, Heineke J, Schmidt VJ, Jantzen F, Brandes RP, Sugden PH, Drexler H, Molkentin JD, Wollert KC. Conditional Transgenic Expression of Fibroblast Growth Factor 9 in the Adult Mouse Heart Reduces Heart Failure Mortality after Myocardial Infarction. Circulation. 2011;123(5):504-U109.

Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, Bolomini-Vittori M, Korf-Klingebiel M, Napp LC, Hansen B, Kanwischer A, Bavendiek U, Beutel G, Hapke M, Sauer MG, Laudanna C, Hogg N, Vestweber D, Wollert KC. Gdf-15 Is an Inhibitor of Leukocyte Integrin Activation Required for Survival after Myocardial Infarction in Mice. Nature Medicine. 2011;17(5):581-U101.

Bonaca MP, Morrow DA, Braunwald E, Cannon CP, Jiang ST, Breher S, Sabatine MS, Kempf T, Wallentin L, Wollert KC. Growth Differentiation Factor-15 and Risk of Recurrent Events in Patients Stabilized after Acute Coronary Syndrome Observations from Prove It-Timi 22. Arteriosclerosis Thrombosis and Vascular Biology. 2011;31(1):203-10.

2010

Wollert KC, Drexler H. Cell Therapy for the Treatment of Coronary Heart Disease: A Critical Appraisal. Nature Reviews Cardiology. 2010;7(4):204-15.

Anand IS, Kempf T, Rector TS, Tapken H, Allhoff T, Jantzen F, Kuskowski M, Cohn JN, Drexler H, Wollert KC. Serial Measurement of Growth-Differentiation Factor-15 in Heart Failure Relation to Disease Severity and Prognosis in the Valsartan Heart Failure Trial. Circulation. 2010;122(14):1387-+.

2009

Widera C, Horn-Wichmann R, Kempf T, Bethmann K, Fiedler B, Sharma S, Lichtinghagen R, Leitolf H, Ivandic B, Katus HA, Giannitsis E, Wollert KC. Circulating Concentrations of Follistatin-Like 1 in Healthy Individuals and Patients with Acute Coronary Syndrome as Assessed by an Immunoluminometric Sandwich Assay. Clinical Chemistry. 2009;55(10):1794-800.

Meyer GP, Wollert KC, Lotz J, Pirr J, Rager U, Lippolt P, Hahn A, Fichtner S, Schaefer A, Arseniev L, Ganser A, Drexler H. Intracoronary Bone Marrow Cell Transfer after Myocardial Infarction: 5-Year Follow-up from the Randomized-Controlled Boost Trial. European Heart Journal. 2009;30(24):2978-84.

2008

Korf-Klingebiel M, Kempf T, Sauer T, Brinkmann E, Fischer P, Meyer GP, Ganser A, Drexler H, Wollert KC. Bone Marrow Cells Are a Rich Source of Growth Factors and Cytokines: Implications for Cell Therapy Trials after Myocardial Infarction. European Heart Journal. 2008;29(23):2851-8.

2007

Wollert KC, Kempf T, Peter T, Olofsson S, James S, Johnston N, Lindahl B, Horn-Wichmann R, Brabant G, Simoons ML, Armstrong PW, Califf RM, Drexler H, Wallentin L. Prognostic Value of Growth-Differentiation Factor-15 in Patients with Non-St-Elevation Acute Coronary Syndrome. Circulation. 2007;115(8):962-71.

Wollert KC, Kempf T, Lagerqvist B, Lindahl B, Olofsson S, Allhoff T, Peter T, Siegbahn A, Venge P, Drexler H, Wallentin L. Growth Differentiation Factor 15 for Risk Stratification and Selection of an Invasive Treatment Strategy in Non-St-Elevation Acute Coronary Syndrome. Circulation. 2007;116(14):1540-8.

Kempf T, Von Haehling S, Cicoira M, Ponikowski P, Filippatos GS, Rozentryt P, Anker SD, Wollert KC. Prognostic Utility of Growth-Differentiation Factor-15 in Patients with Chronic Heart Failure. European Journal of Heart Failure. 2007;6:46-7.

Kempf T, Horn-Wichmann R, Brabant G, Peter T, Allhoff T, Klein G, Drexler H, Johnston N, Wallentin L, Wollert KC. Circulating Concentrations of Growth-Differentiation Factor 15 in Apparently Healthy Elderly Individuals and Patients with Chronic Heart Failure as Assessed by a New Immunoradiometric Sandwich Assay. Clinical Chemistry. 2007;53(2):284-91.

2006

Schaefer A, Meyer GP, Fuchs M, Klein G, Kaplan M, Wollert KC, Drexler H. Impact of Intracoronary Bone Marrow Cell Transfer on Diastolic Function in Patients after Acute Myocardial Infarction: Results from the Boost Trial. European Heart Journal. 2006;27(8):929-35.

Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary Bone Marrow Cell Transfer after Myocardial Infarction - Eighteen Months' Follow-up Data from the Randomized, Controlled Boost (Bone Marrow Transfer to Enhance St-Elevation Infarct Regeneration) Trial. Circulation. 2006;113(10):1287-94.

Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J, Heineke J, Kotlarz D, Xu J, Molkentin JD, Niessen HW, Drexler H, Wollert KC. The Transforming Growth Factor-Beta Superfamily Member Growth-Differentiation Factor-15 Protects the Heart from Ischemia/Reperfusion Injury. Circulation Research. 2006;98(3):351-60.

Fiedler B, Feil R, Hofmann F, Willenbockel C, Drexler H, Smolenski A, Lohmann SM, Wollert KC. Cgmp-Dependent Protein Kinase Type I Inhibits Tab1-P38 Mitogen-Activated Protein Kinase Apoptosis Signaling in Cardiac Myocytes. Journal of Biological Chemistry. 2006;281(43):32831-40.

2005

Wollert KC, Drexler H. Clinical Applications of Stem Cells for the Heart. Circ Res. 2005;96(2):151-63.

Hofmann M, Wollert KC, Meyer GP, Menke A, Arseniev L, Hertenstein B, Ganser A, Knapp WH, Drexler H. Monitoring of Bone Marrow Cell Homing into the Infarcted Human Myocardium. Circulation. 2005;111(17):2198-202.

Heineke J, Ruetten H, Willenbockel C, Gross SC, Naguib M, Schaefer A, Kempf T, Hilfiker-Kleiner D, Caroni P, Kraft T, Kaiser RA, Molkentin JD, Drexler H, Wollert KC. Attenuation of Cardiac Remodeling after Myocardial Infarction by Muscle Lim Protein-Calcineurin Signaling at the Sarcomeric Z-Disc. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(5):1655-60.

2004

Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction: The Boost Randomised Controlled Clinical Trial. Lancet. 2004;364(9429):141-8.

2002

Heineke J, Hilfiker A, Kempf T, Morawietz H, Lohmann SM, Drexler H, Wollert KC. Downregulation of Cytoskeletal Muscle Lim Protein by Nitric Oxide: Impact on Cardiac Myocyte Hypertrophy. Circulation. 2002;106(19):9-.

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