AAV6-mediated cardiac-specific overexpression of ribonucleotide reductase enhances myocardial contractility

Molecular Therapy

Volumn 24, Issue 2, 2016, Pages 240-250

  Kolwicz, Stephen C ^a   Odom, Guy L ^a   Nowakowski, Sarah G ^b   Moussavi Harami, Farid ^c   Chen, Xiaolan ^c   Reinecke, Hans ^a   Hauschka, Stephen D ^c   Murry, Charles E ^a,b,c   Mahairas, Gregory G ^d   Regnier, Michael ^a,b  

^a UNIVERSITY OF WASHINGTON   (United States)

^b University of Washington   (United States)

^c UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^d BEAT Biotherapeutics Corp   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PARVOVIRUS VECTOR; RIBONUCLEOTIDE REDUCTASE; TROPONIN T; RIBONUCLEOSIDE DIPHOSPHATE REDUCTASE; RIBONUCLEOTIDE REDUCTASE M2; TNNT2 PROTEIN, HUMAN;

ADENO ASSOCIATED VIRUS 6; ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ECHOCARDIOGRAPHY; EX VIVO STUDY; HEART FAILURE; HEART LEFT VENTRICLE FUNCTION; HEART MUSCLE CONTRACTILITY; HEART WEIGHT; HISTOPATHOLOGY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; TROPONIN T GENE; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; ADMINISTRATION AND DOSAGE; ANIMAL; ANTIBODY SPECIFICITY; DEPENDOPARVOVIRUS; DISEASE MODEL; GENE THERAPY; GENE VECTOR; GENETICS; HEART CONTRACTION; HEART VENTRICLE; HUMAN; MYOCARDIAL INFARCTION; PATHOPHYSIOLOGY; RAT;

ANIMALS; DEPENDOVIRUS; DISEASE MODELS, ANIMAL; GENETIC THERAPY; GENETIC VECTORS; HEART VENTRICLES; HUMANS; MICE; MYOCARDIAL CONTRACTION; MYOCARDIAL INFARCTION; ORGAN SPECIFICITY; RATS; RIBONUCLEOSIDE DIPHOSPHATE REDUCTASE; RIBONUCLEOTIDE REDUCTASES; TROPONIN T;

EID: 84959495522     PISSN: 15250016     EISSN: 15250024     Source Type: Journal    
DOI: 10.1038/mt.2015.176     Document Type: Article

References (49)

1. Go, AS, Mozaffarian, D, Roger, VL, Benjamin, EJ, Berry, JD, Borden, WB, et al.; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. (2013). Heart disease and stroke statistics-2013 update: a report from the American Heart Association. Circulation 127: e6-E245.
2. McMurray, JJ (2010). Clinical practice. Systolic heart failure. N Engl J Med 362: 228-238.
3. Abraham, WT, Adams, KF, Fonarow, GC, Costanzo, MR, Berkowitz, RL, LeJemtel, TH, et al.; ADHERE Scientific Advisory Committee and Investigators; ADHERE Study Group. (2005). In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol 46: 57-64.
4. Teerlink, JR, Metra, M, Zacà, V, Sabbah, HN, Cotter, G, Gheorghiade, M, et al. (2009). Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond. Heart Fail Rev 14: 243-253.
5. Hajjar, RJ (2013). Potential of gene therapy as a treatment for heart failure. J Clin Invest 123: 53-61.
6. Jessup, M, Greenberg, B, Mancini, D, Cappola, T, Pauly, DF, Jaski, B, et al.; Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) Investigators. (2011). Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation 124: 304-313.
7. Zsebo, K, Yaroshinsky, A, Rudy, JJ, Wagner, K, Greenberg, B, Jessup, M, et al. (2014). Long-Term effects of AAV1/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality. Circ Res 114: 101-108.
8. Morgan, BP, Muci, A, Lu, PP, Qian, X, Tochimoto, T, Smith, WW, et al. (2010). Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin. ACS Med Chem Lett 1: 472-477.
9. Teerlink, Jr. (2009). A novel approach to improve cardiac performance: cardiac myosin activators. Heart Fail Rev 14: 289-298.
10. Teerlink, JR, Clarke, CP, Saikali, KG, Lee, JH, Chen, MM, Escandon, RD, et al. (2011). Dose-Dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study. Lancet 378: 667-675.
11. Regnier, M and Homsher, E (1998). The effect of ATP analogs on posthydrolytic and force development steps in skinned skeletal muscle fibers. Biophys J 74: 3059-3071.
12. Regnier, M, Lee, DM and Homsher, E (1998). ATP analogs and muscle contraction: mechanics and kinetics of nucleoside triphosphate binding and hydrolysis. Biophys J 74: 3044-3058.
13. Regnier, M, Rivera, AJ, Chen, Y and Chase, PB (2000). 2-Deoxy-ATP enhances contractility of rat cardiac muscle. Circ Res 86: 1211-1217.
14. Regnier, M, Martin, H, Barsotti, RJ, Rivera, AJ, Martyn, DA and Clemmens, E (2004). Cross-bridge versus thin filament contributions to the level and rate of force development in cardiac muscle. Biophys J 87: 1815-1824.
15. Adhikari, BB, Regnier, M, Rivera, AJ, Kreutziger, KL and Martyn, DA (2004). Cardiac length dependence of force and force redevelopment kinetics with altered crossbridge cycling. Biophys J 87: 1784-1794.
16. Moussavi-Harami, F, Razumova, MV, Racca, AW, Cheng, Y, Stempien-Otero, A and Regnier, M (2015). 2-Deoxy adenosine triphosphate improves contraction in human end-stage heart failure. J Mol Cell Cardiol 79: 256-263.
17. Korte, FS, Dai, J, Buckley, K, Feest, ER, Adamek, N, Geeves, MA, et al. (2011). Upregulation of cardiomyocyte ribonucleotide reductase increases intracellular 2 deoxy-ATP, contractility and relaxation. J Mol Cell Cardiol 51: 894-901.
18. Nowakowski, SG, Kolwicz, SC, Korte, FS, Luo, Z, Robinson-Hamm, JN, Page, JL, et al. (2013). Transgenic overexpression of ribonucleotide reductase improves cardiac performance. Proc Natl Acad Sci USA 110: 6187-6192.
19. Xu, X, Page, JL, Surtees, JA, Liu, H, Lagedrost, S, Lu, Y, et al. (2008). Broad overexpression of ribonucleotide reductase genes in mice specifically induces lung neoplasms. Cancer Res 68: 2652-2660.
20. Sasano, T, Kikuchi, K, McDonald, AD, Lai, S and Donahue, JK (2007). Targeted highefficiency, homogeneous myocardial gene transfer. J Mol Cell Cardiol 42: 954-961.
21. Gao, G, Bish, LT, Sleeper, MM, Mu, X, Sun, L, Lou, Y, et al. (2011). Transendocardial delivery of AAV6 results in highly efficient and global cardiac gene transfer in rhesus macaques. Hum Gene Ther 22: 979-984.
22. Katz, MG, Fargnoli, AS, Swain, JD, Tomasulo, CE, Ciccarelli, M, Huang, ZM, et al. (2012). AAV6-βARKct gene delivery mediated by molecular cardiac surgery with recirculating delivery (MCARD) in sheep results in robust gene expression and increased adrenergic reserve. J Thorac Cardiovasc Surg 143: 720-726.e3.
23. Evans, JM, Navarro, S, Doki, T, Stewart, JM, Mitsuhashi, N and Kearns-Jonker, M (2012). Gene transfer of heme oxygenase-1 using an adeno-Associated virus serotype 6 vector prolongs cardiac allograft survival. J Transplant 2012: 740653.
24. Raake, PW, Schlegel, P, Ksienzyk, J, Reinkober, J, Barthelmes, J, Schinkel, S, et al. (2013). AAV6.αARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur Heart J 34: 1437-1447.
25. Kadota, S, Carey, J, Reinecke, H, Leggett, J, Teichman, S, Laflamme, MA, et al. (2015). Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure. Eur J Heart Fail 17: 772-781.
26. Ghosh, A, Yue, Y, Lai, Y and Duan, D (2008). A hybrid vector system expands adenoassociated viral vector packaging capacity in a transgene-independent manner. Mol Ther 16: 124-130.
27. Ghosh, A, Yue, Y, Shin, JH and Duan, D (2009). Systemic Trans-splicing adeno-Associated viral delivery efficiently transduces the heart of adult mdx mouse, a model for duchenne muscular dystrophy. Hum Gene Ther 20: 1319-1328.
28. Odom, GL, Gregorevic, P, Allen, JM and Chamberlain, JS (2011). Gene therapy of mdx mice with large truncated dystrophins generated by recombination using rAAV6. Mol Ther 19: 36-45.
29. Aye, Y, Li, M, Long, MJ and Weiss, RS (2015). Ribonucleotide reductase and cancer: biological mechanisms and targeted therapies. Oncogene 34: 2011-2021.
30. Caras, IW and Martin, DW Jr. (1988). Molecular cloning of the cDNA for a mutant mouse ribonucleotide reductase M1 that produces a dominant mutator phenotype in mammalian cells. Mol Cell Biol 8: 2698-2704.
31. Jordan, A and Reichard, P (1998). Ribonucleotide reductases. Annu Rev Biochem 67: 71-98.
32. Reichard, P, Eliasson, R, Ingemarson, R and Thelander, L (2000). Cross-Talk between the allosteric effector-binding sites in mouse ribonucleotide reductase. J Biol Chem 275: 33021-33026.
33. Fairman, JW, Wijerathna, SR, Ahmad, MF, Xu, H, Nakano, R, Jha, S, et al. (2011). Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization. Nat Struct Mol Biol 18: 316-322.
34. Kreutziger, KL, Piroddi, N, McMichael, JT, Tesi, C, Poggesi, C and Regnier, M (2011). Calcium binding kinetics of troponin C strongly modulate cooperative activation and tension kinetics in cardiac muscle. J Mol Cell Cardiol 50: 165-174.
35. Regnier, M, Rivera, AJ, Chase, PB, Smillie, LB and Sorenson, MM (1999). Regulation of skeletal muscle tension redevelopment by troponin C constructs with different Ca2+affinities. Biophys J 76: 2664-2672.
36. Nowakowski, SG, Adamek, N, Geeves, MA, Gay, E, Kolwicz Jr, SC, Murry, CE, et al. (2013). 2-Deoxy-ATP alters myosin structure to enhance cross-bridge cycling and improve cardiac function. Biophys J 104: 17a.
37. McDonald, KS and Moss, RL (2000). Strongly binding myosin crossbridges regulate loaded shortening and power output in cardiac myocytes. Circ Res 87: 768-773.
38. Dobesh, DP, Konhilas, JP and de Tombe, PP (2002). Cooperative activation in cardiac muscle: impact of sarcomere length. Am J Physiol Heart Circ Physiol 282: H1055-H1062.
39. Masson, R, Nicklin, SA, Craig, MA, McBride, M, Gilday, K, Gregorevic, P, et al. (2009). Onset of experimental severe cardiac fibrosis is mediated by overexpression of Angiotensin-converting enzyme 2. Hypertension 53: 694-700.
40. Gao, S, Ho, D, Vatner, DE and Vatner, SF (2011). Echocardiography in Mice. Curr Protoc Mouse Biol 1: 71-83.
41. Pachon, RE, Scharf, BA, Vatner, DE and Vatner, SF (2015). Best anesthetics for assessing left ventricular systolic function by echocardiography in mice. Am J Physiol Heart Circ Physiol 308: H1525-H1529.
42. Lundy, SD, Murphy, SA, Dupras, SK, Dai, J, Murry, CE, Laflamme, MA, et al. (2014). Cell-based delivery of dATP via gap junctions enhances cardiac contractility. J Mol Cell Cardiol 72: 350-359.
43. Mar, JH, Antin, PB, Cooper, TA and Ordahl, CP (1988). Analysis of the upstream regions governing expression of the chicken cardiac troponin T gene in embryonic cardiac and skeletal muscle cells. J Cell Biol 107: 573-585.
44. Wang, G, Yeh, HI and Lin, JJ (1994). Characterization of cis-regulating elements and trans-Activating factors of the rat cardiac troponin T gene. J Biol Chem 269: 30595-30603.
45. Kim, JH, Lee, SR, Li, LH, Park, HJ, Park, JH, Lee, KY, et al. (2011). High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice. PLoS One 6: e18556.
46. Halbert, CL, Allen, JM and Miller, AD (2001). Adeno-Associated virus type 6 (AAV6) vectors mediate efficient transduction of airway epithelial cells in mouse lungs compared to that of AAV2 vectors. J Virol 75: 6615-6624.
47. Blankinship, MJ, Gregorevic, P, Allen, JM, Harper, SQ, Harper, H, Halbert, CL, et al. (2004). Efficient transduction of skeletal muscle using vectors based on adenoassociated virus serotype 6. Mol Ther 10: 671-678.
48. Gregorevic, P, Blankinship, MJ, Allen, JM, Crawford, RW, Meuse, L, Miller, DG, et al. (2004). Systemic delivery of genes to striated muscles using adeno-Associated viral vectors. Nat Med 10: 828-834.
49. Kolwicz, SC, Jr, Tian, R (2010). Assessment of cardiac function and energetics in isolated mouse hearts using 31P NMR spectroscopy. J Vis Exp 42: e2069.