Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model

Science Translational Medicine

Volumn 3, Issue 92, 2011, Pages

  Pleger, Sven T ^a   Shan, Changguang ^a   Ksienzyk, Jan ^a   Bekeredjian, Raffi ^a   Boekstegers, Peter ^b   Hinkel, Rabea ^b   Schinkel, Stefanie ^a   Leuchs, Barbara ^c   Ludwig, Jochen ^a   Qiu, Gang ^d   Weber, Christophe ^a   Raake, Philip ^a   Koch, Walter J ^d   Katus, Hugo A ^a   Müller, Oliver J ^a   Most, Patrick ^a,d  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^d THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; CALCIUM ION; COMPLEMENTARY DNA; CREATINE PHOSPHATE; LUCIFERASE; MESSENGER RNA; NICOTINAMIDE ADENINE DINUCLEOTIDE; PARVOVIRUS VECTOR; PROTEIN S 100; PROTEIN S100A1; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; CALCIUM; S100A1 PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BALLOON OCCLUSION; CALCIUM CELL LEVEL; CARDIOVASCULAR GENE THERAPY; CELL ISOLATION; CONGESTIVE HEART FAILURE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; GENE; GENE EXPRESSION; HEART FUNCTION; HEART INFARCTION; HEART MUSCLE CELL; HOMEOSTASIS; HUMAN; MITOCHONDRIAL ENERGY TRANSFER; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; S100A1 GENE; SWINE; TRANSGENE; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; ADENO ASSOCIATED VIRUS; ANIMAL; ANTIBODY SPECIFICITY; BLOOD; DISEASE MODEL; ENERGY METABOLISM; GENE THERAPY; GENE TRANSFER; GENETICS; HEART FAILURE; HEART FUNCTION TEST; HEART MUSCLE; HEART MUSCLE ISCHEMIA; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; SARCOPLASMIC RETICULUM;

ANIMALS; BIOLOGICAL MARKERS; CALCIUM; DEPENDOVIRUS; DISEASE MODELS, ANIMAL; ENERGY METABOLISM; GENE THERAPY; GENE TRANSFER TECHNIQUES; HEART FAILURE; HEART FUNCTION TESTS; HOMEOSTASIS; HUMANS; MYOCARDIAL INFARCTION; MYOCARDIAL ISCHEMIA; MYOCARDIUM; MYOCYTES, CARDIAC; ORGAN SPECIFICITY; S100 PROTEINS; SARCOPLASMIC RETICULUM; SUS SCROFA;

EID: 79960696509     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3002097     Document Type: Article

References (49)

1. V. L. Roger, A. S. Go, D. M. Lloyd-Jones, R. J. Adams, J. D. Berry, T. M. Brown, M. R. Carnethon, S. Dai, G. de Simone, E. S. Ford, C. S. Fox, H. J. Fullerton, C. Gillespie, K. J. Greenlund, S. M. Hailpern, J. A. Heit, P. M. Ho, V. J. Howard, B. M. Kissela, S. J. Kittner, D. T. Lackland, J. H. Lichtman, L. D. Lisabeth, D. M. Makuc, G. M. Marcus, A. Marelli, D. B. Matchar, M. M. McDermott, J. B. Meigs, C. S. Moy, D. Mozaffarian, M. E. Mussolino, G. Nichol, N. P. Paynter, W. D. Rosamond, P. D. Sorlie, R. S. Stafford, T. N. Turan, M. B. Turner, N. D. Wong, J. Wylie-Rosett; American Heart Association Statistics Committee and Stroke Statistics Subcommittee, Heart disease and stroke statistics - 2011 update: A report from the American Heart Association. Circulation 123, e18-e209 (2011).
2. J. J. McMurray, Clinical practice. Systolic heart failure. N. Engl. J. Med. 362, 228-238 (2010).
3. B. A. Groenning, J. C. Nilsson, L. Sondergaard, T. Fritz-Hansen, H. B. Larsson, P. R. Hildebrandt, Antiremodeling effects on the left ventricle during b-blockade with metoprolol in the treatment of chronic heart failure. J. Am. Coll. Cardiol. 36, 2072-2080 (2000).
4. The RESOLVD Investigators, Effects of metoprolol CR in patients with ischemic and dilated cardiomyopathy: The randomized evaluation of strategies for left ventricular dysfunction pilot study. Circulation 101, 378-384 (2000).
5. E. Vizzardi, A. D'Aloia, R. Giubbini, T. Bordonali, S. Bugatti, N. Pezzali, A. Romeo, A. Dei Cas, M. Metra, L. Dei Cas, Effect of spironolactone on left ventricular ejection fraction and volumes in patients with class I or II heart failure. Am. J. Cardiol. 106, 1292-1296 (2010).
6. M. D. Flather, S. Yusuf, L. Køber, M. Pfeffer, A. Hall, G. Murray, C. Torp-Pedersen, S. Ball, J. Pogue, L. Moyé, E. Braunwald, Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: A systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 355, 1575-1581 (2000).
7. B. Greenberg, M. A. Quinones, C. Koilpillai, M. Limacher, D. Shindler, C. Benedict, B. Shelton, Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy. Circulation 91, 2573-2581 (1995).
8. K. K. Ho, J. L. Pinsky, W. B. Kannel, D. Levy, The epidemiology of heart failure: The Framingham Study. J. Am. Coll. Cardiol. 22, 6A-13A (1993).
9. S. T. Pleger, M. Boucher, P. Most, W. J. Koch, Targeting myocardial β-adrenergic receptor signaling and calcium cycling for heart failure gene therapy. J. Card. Fail. 13, 401-414 (2007).
10. D. M. Bers, Cardiac excitation-contraction coupling. Nature 415, 198-205 (2002).
11. C. Kraus,D. Rohde, C. Weidenhammer, G. Qiu, S. T. Pleger, M. Voelkers, M. Boerries, A. Remppis, H. A. Katus, P. Most, S100A1 in cardiovascular health and disease: Closing the gap between basic science and clinical therapy. J. Mol. Cell. Cardiol. 47, 445-455 (2009).
12. M. Boerries, P.Most, J. R. Gledhill, J. E. Walker, H. A. Katus, W. J. Koch,U. Aebi, C. A. Schoenenberger, Ca2+-dependent interaction of S100A1 with F1-ATPase leads to an increased ATP content in cardiomyocytes. Mol. Cell. Biol. 27, 4365-4373 (2007).
13. P. Most, J. Bernotat, P. Ehlermann, S. T. Pleger, M. Reppel, M. Börries, F. Niroomand, B. Pieske, P. M. Janssen, T. Eschenhagen, P. Karczewski, G. L. Smith, W. J. Koch, H. A. Katus, A. Remppis, S100A1: A regulator of myocardial contractility. Proc. Natl. Acad. Sci. U.S.A. 98, 13889-13894 (2001).
14. P. Most, A. Remppis, S. T. Pleger, E. Löffler, P. Ehlermann, J. Bernotat, C. Kleuss, J. Heierhorst, P. Ruiz, H. Witt, P. Karczewski, L. Mao, H. A. Rockman, S. J. Duncan, H. A. Katus, W. J. Koch, Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance. J. Biol. Chem. 278, 33809-33817 (2003).
15. P. Most, H. Seifert, E. Gao, H. Funakoshi, M. Völkers, J. Heierhorst, A. Remppis, S. T. Pleger, B. R. DeGeorge Jr., A. D. Eckhart, A. M. Feldman, W. J. Koch, Cardiac S100A1 protein levels determine contractile performance and propensity toward heart failure after myocardial infarction. Circulation 114, 1258-1268 (2006).
16. J. N. Tsoporis, A. Marks, D. B. Zimmer, C. McMahon, T. G. Parker, The myocardial protein S100A1 plays a role in the maintenance of normal gene expression in the adult heart. Mol. Cell. Biochem. 242, 27-33 (2003).
17. M. Völkers, C. M. Loughrey, N. Macquaide, A. Remppis, B. R. DeGeorge Jr., F. V. Wegner, O. Friedrich, R. H. Fink, W. J. Koch, G. L. Smith, P. Most, S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes. Cell Calcium 41, 135-143 (2007).
18. K. Gusev, G. E. Ackermann, C. W. Heizmann, E. Niggli, Ca2+ signaling in mouse cardiomyocytes with ablated S100A1 protein. Gen. Physiol. Biophys. 28, 371-383 (2009).
19. N. T. Wright, B. R. Cannon, D. B. Zimmer, D. J. Weber, S100A1: Structure, function, and therapeutic potential. Curr. Chem. Biol. 3, 138-145 (2009).
20. P. Most, S. T. Pleger, M. Völkers, B. Heidt, M. Boerries, D. Weichenhan, E. Löffler, P. M. Janssen, A. D. Eckhart, J. Martini, M. L. Williams, H. A. Katus, A. Remppis, W. J. Koch, Cardiac adenoviral S100A1 gene delivery rescues failing myocardium. J. Clin. Invest. 114, 1550-1563 (2004).
21. S. T. Pleger, P. Most, M. Boucher, S. Soltys, J. K. Chuprun, W. Pleger, E. Gao, A. Dasgupta, G. Rengo, A. Remppis, H. A. Katus, A. D. Eckhart, J. E. Rabinowitz,W. J. Koch, Stablemyocardial-specific AAV6-S100A1 gene therapy results in chronic functional heart failure rescue. Circulation 115, 2506-2515 (2007).
22. S. T. Pleger, A. Remppis, B. Heidt,M. Völkers, J. K. Chuprun,M. Kuhn, R. H. Zhou, E. Gao, G. Szabo, D. Weichenhan, O. J. Müller, A. D. Eckhart, H. A. Katus, W. J. Koch, P. Most, S100A1 gene therapy preserves in vivo cardiac function after myocardial infarction. Mol. Ther. 12, 1120-1129 (2005).
23. A. Remppis, T. Greten, B. W. Schäfer, P. Hunziker, P. Erne, H. A. Katus, C. W. Heizmann, Altered expression of the Ca2+-binding protein S100A1 in human cardiomyopathy. Biochim. Biophys. Acta 1313, 253-257 (1996).
24. J. F. Desjardins, A. Pourdjabbar, A. Quan, H. Leong-Poi, K. Teichert-Kuliszewska, S. Verma, T. G. Parker, Lack of S100A1 in mice confers a gender-dependent hypertensive phenotype and increased mortality after myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 296, H1457-H1465 (2009).
25. X. J. Du, T. J. Cole, N. Tenis, X. M. Gao, F. Köntgen, B. E. Kemp, J. Heierhorst, Impaired cardiac contractility response to hemodynamic stress in S100A1-deficient mice. Mol. Cell. Biol. 22, 2821-2829 (2002).
26. J. A. Dixon, F. G. Spinale, Large animal models of heart failure: A critical link in the translation of basic science to clinical practice. Circ. Heart Fail. 2, 262-271 (2009).
27. L. Hove-Madsen, D. M. Bers, Sarcoplasmic reticulum Ca2+ uptake and thapsigargin sensitivity in permeabilized rabbit and rat ventricular myocytes. Circ. Res. 73, 820-828 (1993).
28. J. James, Y. Zhang, K. Wright, S. Witt, E. Glascock, H. Osinska, R. Klevitsky, L. Martin, K. Yager, A. Sanbe, J. Robbins, Transgenic rabbits expressing mutant essential light chain do not develop hypertrophic cardiomyopathy. J. Mol. Cell. Cardiol. 34, 873-882 (2002).
29. 31P-MRS study. Circulation 94, 1089-1100 (1996).
30. H. L. Brinks, D. Rohde, M. Voelkers, G. Qiu, S. T. Pleger, N. Herzog, J. Rabinowitz, A. Ruhparwar, S. Silvestry, C. Kraus, P. Mather, H. A. Katus, W. J. Koch, P. Most, S100A1 genetically targeted therapy reverses dysfunction of human failing myocardium. J. Am. Coll. Cardiol. 57, E188 (2011).
31. O. J. Müller, F. Kaul, M. D. Weitzman, R. Pasqualini, W. Arap, J. A. Kleinschmidt, M. Trepel, Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. Nat. Biotechnol. 21, 1040-1046 (2003).
32. G. von Degenfeld, P. Raake, C. Kupatt, C. Lebherz, R. Hinkel, F. J. Gildehaus, W. Münzing, A. Kranz, J. Waltenberger, M. Simoes, M. Schwaiger, E. Thein, P. Boekstegers, Selective pressure-regulated retroinfusion of fibroblast growth factor-2 into the coronary vein enhances regional myocardial blood flow and function in pigs with chronic myocardial ischemia. J. Am. Coll. Cardiol. 42, 1120-1128 (2003).
33. K. E. Yutzey, J. Robbins, Principles of genetic murine models for cardiac disease. Circulation 115, 792-799 (2007).
34. K. Haghighi, F. Kolokathis, L. Pater, R. A. Lynch, M. Asahi, A. O. Gramolini, G. C. Fan, D. Tsiapras, H. S. Hahn, S. Adamopoulos, S. B. Liggett, G. W. Dorn II, D. H. MacLennan, D. T. Kremastinos, E. G. Kranias, Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. J. Clin. Invest. 111, 869-876 (2003).
35. O. J. Müller, B. Leuchs, S. T. Pleger, D. Grimm, W. M. Franz, H. A. Katus, J. A. Kleinschmidt, Improved cardiac gene transfer by transcriptional and transductional targeting of adeno-associated viral vectors. Cardiovasc. Res. 70, 70-78 (2006).
36. P. Most, W. J. Koch, Sealing the leak, healing the heart. Nat. Med. 9, 993-994 (2003).
37. J. K. Gwathmey, L. Copelas, R. MacKinnon, F. J. Schoen, M. D. Feldman, W. Grossman, J. P. Morgan, Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ. Res. 61, 70-76 (1987).
38. W. J. Koch, R. J. Lefkowitz, H. A. Rockman, Functional consequences of altering myocardial adrenergic receptor signaling. Annu. Rev. Physiol. 62, 237-260 (2000).
39. G. M. Felker, C. M. O'Connor, Inotropic therapy for heart failure: An evidence-based approach. Am. Heart J. 142, 393-401 (2001).
40. D. D. Shin, F. Brandimarte, L. De Luca, H. N. Sabbah, G. C. Fonarow, G. Filippatos, M. Komajda, M. Gheorghiade, Review of current and investigational pharmacologic agents for acute heart failure syndromes. Am. J. Cardiol. 99, 4A-23A (2007).
41. R. S. Balaban, Cardiac energy metabolism homeostasis: Role of cytosolic calcium. J. Mol. Cell. Cardiol. 34, 1259-1271 (2002).
42. R. Ventura-Clapier, A. Garnier, V. Veksler, Energy metabolism in heart failure. J. Physiol. 555, 1-13 (2004).
43. R. J. Hajjar, K. Zsebo, L. Deckelbaum, C. Thompson, J. Rudy, A. Yaroshinsky, H. Ly, Y. Kawase, K. Wagner, K. Borow, B. Jaski, B. London, B. Greenberg, D. F. Pauly, R. Patten, R. Starling, D. Mancini, M. Jessup, Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J. Card. Fail. 14, 355-367 (2008).
44. F. S. Villanueva, E. W. Gertz, M. Csikari, G. Pulido, D. Fisher, J. Sklenar, Detection of coronary artery stenosis with power Doppler imaging. Circulation 103, 2624-2630 (2001).
45. R. Bekeredjian, S. Chen, P. A. Frenkel, P. A. Grayburn, R. V. Shohet, Ultrasound-targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart. Circulation 108, 1022-1026 (2003).
46. G. A. Peeters, M. C. Sanguinetti, Y. Eki, H. Konarzewska, D. G. Renlund, S. V. Karwande, W. H. Barry, Method for isolation of human ventricular myocytes from single endocardial and epicardial biopsies. Am. J. Physiol. 268, H1757-H1764 (1995).
47. http://www.stanford.edu/~cpatton/maxc.html
48. http://www.nal.usda.gov/awic/pubs/swine/swine.htm
49. Acknowledgments: We thank R. Eudenbach, J. Kleinschmidt, and the German Cancer Research Center vector core production unit for generating high-titer AAV vector stocks. Funding: This work was supported by NIH grants R01HL92130 and R01HL92130-02S1 (P.M.) and P01HL075443, R01HL56205, and R01HL061690 (W.J.K.); Deutsche Forschungsgemeinschaft grants 1654/3-2 (O.J.M.) and 562/1-1 (P.M. and S.T.P.); Bundesministerium für Bildung und Forschung grant 01GU0527 (P.M., O.J.M., P.B., and H.A.K.); and BioFuture grant (R.B.). Author contributions: S.T.P. and P.M. wrote the manuscript. S.T.P., C.S., J.K., P.R., W.J.K., H.A.K., O.J.M., and P.M. designed the experiments. S.T.P., C.S., J.K., R.B., P.B., R.H., S.S., B.L., J.L., C.W., and O.J.M. performed the experiments and analyzed the data. G.Q. conducted biochemical assays. Competing interests: P.M. and H.A.K. have filed U.S. and EU patent applications on the therapeutic use of the S100A1 protein to treat heart failure.