(Circulation. 1997;95:423-429.)
© 1997 American Heart Association, Inc.
Articles |
Physiological Effects of Adenoviral Gene Transfer of Sarcoplasmic Reticulum Calcium ATPase in Isolated Rat Myocytes
the Cardiovascular Research Center and Cardiac Unit (R.J.H., A.R.), Medical Services, and Department of Preventive Medicine (J.X.K.), Massachusetts General Hospital, the Cardiovascular Disease and Muscle Research Laboratories (J.K.G.), and Harvard Medical School, Boston, Mass.
Correspondence to Anthony Rosenzweig, MD, Cardiovascular Research Center, Massachusetts General Hospital East, 149 13th St, Charlestown, MA 02107.
Background In myocardial cells, relaxation is governed primarily by the sarcoplasmic reticulum (SR) Ca2+-ATPase transporting enzyme, which regulates Ca2+ sequestration into the SR. Human and experimental cardiomyopathies are associated with reduced SR Ca2+-ATPase activity.
Methods and Results To modify intracellular calcium mobilization, we created a recombinant adenovirus designed to overexpress the cardiac SR Ca2+-ATPase (SERCA2a) under the control of the Rous sarcoma virus (RSV). In neonatal rat myocytes, Ad.RSV.SERCA2a increased the expression of SERCA2a in a concentration-dependent and time-dependent fashion. Enhancement of SR Ca2+-ATPase activity was even greater than increases in SERCA2a protein content in cells infected with Ad.RSV.SERCA2a for 48 hours at a multiplicity of infection (MOI) from 0.1 to 10.0 pfu/cell. Intracellular calcium transients measured in the neonatal cells infected with Ad.RSV.SERCA2a were characterized by an abbreviation of the relaxation phase, an increase in peak [Ca2+]i release, and a decrease in resting [Ca2+]i levels. Ad.RSV.SERCA2a also enhanced the contraction of the myocardial cells as detected by shortening measurements.
Conclusions We found that adenovirus-mediated gene transfer of SR Ca2+-ATPase can modify intracellular calcium handling and shortening in myocardial cells. Such vectors should be useful in examining the role of reduced SERCA2a activity in the pathophysiology of heart failure and in developing strategies for gene therapy.
Key Words: genes • calcium • sarcoplasmic reticulum • SERCA2a
This article has been cited by other articles:
 |
|
 |
|
  E. Vafiadaki, D. A. Arvanitis, S. N. Pagakis, V. Papalouka, D. Sanoudou, A. Kontrogianni-Konstantopoulos, and E. G. Kranias The Anti-apoptotic Protein HAX-1 Interacts with SERCA2 and Regulates Its Protein Levels to Promote Cell Survival Mol. Biol. Cell, January 1, 2009; 20(1): 306 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Davis, M. V. Westfall, D. Townsend, M. Blankinship, T. J. Herron, G. Guerrero-Serna, W. Wang, E. Devaney, and J. M. Metzger Designing Heart Performance by Gene Transfer Physiol Rev, October 1, 2008; 88(4): 1567 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Day, P. Coutu, W. Wang, T. Herron, I. Turner, M. Shillingford, N. C. LaCross, K. L. Converso, L. Piao, J. Li, et al. Cardiac-directed parvalbumin transgene expression in mice shows marked heart rate dependence of delayed Ca2+ buffering action Physiol Genomics, May 1, 2008; 33(3): 312 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kawase, H. Q. Ly, F. Prunier, D. Lebeche, Y. Shi, H. Jin, L. Hadri, R. Yoneyama, K. Hoshino, Y. Takewa, et al. Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure. J. Am. Coll. Cardiol., March 18, 2008; 51(11): 1112 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Smith Matters of the heart: the physiology of cardiac function and failure Exp Physiol, November 1, 2007; 92(6): 973 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sakata, D. Lebeche, N. Sakata, Y. Sakata, E. R. Chemaly, L. F. Liang, Y. Takewa, D. Jeong, W. J. Park, Y. Kawase, et al. Targeted gene transfer increases contractility and decreases oxygen cost of contractility in normal rat hearts Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2356 - H2363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Maier, C. Wahl-Schott, W. Horn, S. Weichert, C. Pagel, S. Wagner, N. Dybkova, O. J. Muller, M. Nabauer, W.-M. Franz, et al. Increased SR Ca2+ cycling contributes to improved contractile performance in SERCA2a-overexpressing transgenic rats Cardiovasc Res, September 1, 2005; 67(4): 636 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Ahlers, J. Song, J. Wang, X.-Q. Zhang, L. L. Carl, G. M. Tadros, L. I. Rothblum, and J. Y. Cheung Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes J Appl Physiol, June 1, 2005; 98(6): 2169 - 2176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Coutu and J. M. Metzger Genetic manipulation of calcium-handling proteins in cardiac myocytes. I. Experimental studies Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H601 - H612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Coutu and J. M. Metzger Genetic manipulation of calcium-handling proteins in cardiac myocytes. II. Mathematical modeling studies Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H613 - H631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Teucher, J. Prestle, T. Seidler, S. Currie, E. B. Elliott, D. F. Reynolds, P. Schott, S. Wagner, H. Kogler, G. Inesi, et al. Excessive Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase Expression Causes Increased Sarcoplasmic Reticulum Ca2+ Uptake but Decreases Myocyte Shortening Circulation, December 7, 2004; 110(23): 3553 - 3559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Seth, C. Sumbilla, S. P. Mullen, D. Lewis, M. G. Klein, A. Hussain, J. Soboloff, D. L. Gill, and G. Inesi Sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) gene silencing and remodeling of the Ca2+ signaling mechanism in cardiac myocytes PNAS, November 23, 2004; 101(47): 16683 - 16688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Hirsch, A. R. Borton, F. P. Albayya, M. W. Russell, R. G. Ohye, and J. M. Metzger Comparative analysis of parvalbumin and SERCA2a cardiac myocyte gene transfer in a large animal model of diastolic dysfunction Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2314 - H2321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. MELO, A. S. PACHORI, D. KONG, M. GNECCHI, K. WANG, R. E. PRATT, and V. J. DZAU Gene and cell-based therapies for heart disease FASEB J, April 1, 2004; 18(6): 648 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ma, C. M. Sumbilla, I. K. G. Farrance, M. G. Klein, and G. Inesi Cell-specific expression of SERCA, the exogenous Ca2+ transport ATPase, in cardiac myocytes Am J Physiol Cell Physiol, March 1, 2004; 286(3): C556 - C564. [Abstract] [Full Text]
|
|
|
|
|
|
H. C. Champion, D. Georgakopoulos, S. Haldar, L. Wang, Y. Wang, and D. A. Kass Robust Adenoviral and Adeno-Associated Viral Gene Transfer to the In Vivo Murine Heart: Application to Study of Phospholamban Physiology Circulation, December 2, 2003; 108(22): 2790 - 2797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Brunner, S. A. Kodirov, G. F. Mitchell, P. D. Buckett, K. Shibata, E. J. Folco, L. Baker, G. Salama, D. P. Chan, J. Zhou, et al. In vivo gene transfer of Kv1.5 normalizes action potential duration and shortens QT interval in mice with long QT phenotype Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H194 - H203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. del Monte and R. J Hajjar Targeting calcium cycling proteins in heart failure through gene transfer J. Physiol., January 1, 2003; 546(1): 49 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Del Monte, K. Butler, W. Boecker, J. K. Gwathmey, and R. J. Hajjar Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure Physiol Genomics, April 10, 2002; 9(1): 49 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsui, J. Tao, F. del Monte, K.-H. Lee, L. Li, M. Picard, T. L. Force, T. F. Franke, R. J. Hajjar, and A. Rosenzweig Akt Activation Preserves Cardiac Function and Prevents Injury After Transient Cardiac Ischemia In Vivo Circulation, July 17, 2001; 104(3): 330 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. del Monte, R. J. Hajjar, S. E. Harding, and G. Inesi Overwhelming Evidence of the Beneficial Effects of SERCA Gene Transfer in Heart Failure Response Circ. Res., June 8, 2001; 88 (11): e66 - e67. [Full Text] [PDF]
|
|
|
|
|
|
Z. B. Kang, Y. Ge, Z. Chen, J. Cluette-Brown, M. Laposata, A. Leaf, and J. X. Kang Adenoviral gene transfer of Caenorhabditis elegansn-3 fatty acid desaturase optimizes fatty acid composition in mammalian cells PNAS, March 16, 2001; (2001) 61040198. [Abstract] [Full Text]
|
|
|
|
|
|
M. Periasamy Adenoviral-Mediated SERCA Gene Transfer Into Cardiac Myocytes : How Much Is Too Much? Circ. Res., March 2, 2001; 88(4): 373 - 375. [Full Text] [PDF]
|
|
|
|
|
|
J. M. O'Donnell, C. M. Sumbilla, H. Ma, I. K. G. Farrance, M. Cavagna, M. G. Klein, and G. Inesi Tight Control of Exogenous SERCA Expression Is Required to Obtain Acceleration of Calcium Transients With Minimal Cytotoxic Effects in Cardiac Myocytes Circ. Res., March 2, 2001; 88(4): 415 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Dzau, M. J. Mann, A. Ehsan, and D. P. Griese Gene therapy and genomic strategies for cardiovascular surgery: The emerging field of surgiomics J. Thorac. Cardiovasc. Surg., February 1, 2001; 121(2): 0206 - 216. [Full Text] [PDF]
|
|
|
|
|
|
N. Chossat, F. Griscelli, P. Jourdon, D. Logeart, T. Ragot, M. Heimburger, M. Perricaudet, A.-M. Lompre, S. Hatem, and J.-J. Mercadier Adenoviral SERCA1a gene transfer to adult rat ventricular myocytes induces physiological changes in calcium handling Cardiovasc Res, February 1, 2001; 49(2): 288 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cavagna, J M. O'Donnell, C. Sumbilla, G. Inesi, and M. G Klein Exogenous Ca2+-ATPase isoform effects on Ca2+ transients of embryonic chicken and neonatal rat cardiac myocytes J. Physiol., October 1, 2000; 528(1): 53 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Hajjar, F. del Monte, T. Matsui, and A. Rosenzweig Prospects for Gene Therapy for Heart Failure Circ. Res., March 31, 2000; 86(6): 616 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Schmidt, F. del Monte, M. I. Miyamoto, T. Matsui, J. K. Gwathmey, A. Rosenzweig, and R. J. Hajjar Restoration of Diastolic Function in Senescent Rat Hearts Through Adenoviral Gene Transfer of Sarcoplasmic Reticulum Ca2+-ATPase Circulation, February 22, 2000; 101(7): 790 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Miyamoto, F. del Monte, U. Schmidt, T. S. DiSalvo, Z. B. Kang, T. Matsui, J. L. Guerrero, J. K. Gwathmey, A. Rosenzweig, and R. J. Hajjar Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure PNAS, January 18, 2000; 97(2): 793 - 798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. del Monte, S. E. Harding, U. Schmidt, T. Matsui, Z. B. Kang, G. W. Dec, J. K. Gwathmey, A. Rosenzweig, and R. J. Hajjar Restoration of Contractile Function in Isolated Cardiomyocytes From Failing Human Hearts by Gene Transfer of SERCA2a Circulation, December 7, 1999; 100(23): 2308 - 2311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsui, L. Li, F. del Monte, Y. Fukui, T. F. Franke, R. J. Hajjar, and A. Rosenzweig Adenoviral Gene Transfer of Activated Phosphatidylinositol 3'-Kinase and Akt Inhibits Apoptosis of Hypoxic Cardiomyocytes In Vitro Circulation, December 7, 1999; 100(23): 2373 - 2379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sumbilla, M. Cavagna, L. Zhong, H. Ma, D. Lewis, I. Farrance, and G. Inesi Comparison of SERCA1 and SERCA2a expressed in COS-1 cells and cardiac myocytes Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2381 - H2391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Das, R. M. Engelman, N. Maulik, J. A. Rousou, J. E. Flack III, and D. W. Deaton Molecular targets of gene therapy Ann. Thorac. Surg., November 1, 1999; 68(5): 1929 - 1933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. He, M. Meyer, J. L. Martin, P. M. McDonough, P. Ho, X. Lou, W. Y. W. Lew, R. Hilal-Dandan, and W. H. Dillmann Effects of Mutant and Antisense RNA of Phospholamban on SR Ca2+-ATPase Activity and Cardiac Myocyte Contractility Circulation, August 31, 1999; 100(9): 974 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-L. Laugwitz, M. Ungerer, T. Schoneberg, H.-J. Weig, K. Kronsbein, A. Moretti, K. Hoffmann, M. Seyfarth, G. Schultz, and A. Schomig Adenoviral Gene Transfer of the Human V2 Vasopressin Receptor Improves Contractile Force of Rat Cardiomyocytes Circulation, February 23, 1999; 99(7): 925 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Baker, K. Hashimoto, I. L. Grupp, Y. Ji, T. Reed, E. Loukianov, G. Grupp, A. Bhagwhat, B. Hoit, R. Walsh, et al. Targeted Overexpression of the Sarcoplasmic Reticulum Ca2+-ATPase Increases Cardiac Contractility in Transgenic Mouse Hearts Circ. Res., December 14, 1998; 83(12): 1205 - 1214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Anger, A.-M. Lompre, O. Vallot, F. Marotte, L. Rappaport, and J.-L. S. MD Cellular Distribution of Ca2+ Pumps and Ca2+ Release Channels in Rat Cardiac Hypertrophy Induced by Aortic Stenosis Circulation, December 1, 1998; 98(22): 2477 - 2486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Loukianov, Y. Ji, I. L. Grupp, D. L. Kirkpatrick, D. L. Baker, T. Loukianova, G. Grupp, J. Lytton, R. A. Walsh, and M. Periasamy Enhanced Myocardial Contractility and Increased Ca2+ Transport Function in Transgenic Hearts Expressing the Fast-Twitch Skeletal Muscle Sarcoplasmic Reticulum Ca2+-ATPase Circ. Res., November 2, 1998; 83(9): 889 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Hasenfuss Calcium Pump Overexpression and Myocardial Function : Implications for Gene Therapy of Myocardial Failure Circ. Res., November 2, 1998; 83(9): 966 - 968. [Full Text] [PDF]
|
|
|
|
|
|
B. S. Cain, D. R. Meldrum, K. S. Joo, J.-F. Wang, X. Meng, J. C. Cleveland Jr., A. Banerjee, and A. H. Harken Human SERCA2a levels correlate inversely with age in senescent human myocardium J. Am. Coll. Cardiol., August 1, 1998; 32(2): 458 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Igarashi-Saito, H. Tsutsui, S. Yamamoto, M. Takahashi, S. Kinugawa, H. Tagawa, M. Usui, M. Yamamoto, K. Egashira, and A. Takeshita Role of SR Ca2+-ATPase in contractile dysfunction of myocytes in tachycardia-induced heart failure Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H31 - H40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Hajjar, U. Schmidt, T. Matsui, J. L. Guerrero, K.-H. Lee, J. K. Gwathmey, G. W. Dec, M. J. Semigran, and A. Rosenzweig Modulation of ventricular function through gene transfer in vivo PNAS, April 28, 1998; 95(9): 5251 - 5256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Inesi, D. Lewis, C. Sumbilla, A. Nandi, C. Strock, K. W. Huff, T. B. Rogers, D. C. Johns, P. D. Kessler, and C. P. Ordahl Cell-specific promoter in adenovirus vector for transgenic expression of SERCA1 ATPase in cardiac myocytes Am J Physiol Cell Physiol, March 1, 1998; 274(3): C645 - C653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Meyer and W. H Dillmann Sarcoplasmic reticulum Ca2+-ATPase overexpression by adenovirus mediated gene transfer and in transgenic mice Cardiovasc Res, February 1, 1998; 37(2): 360 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P de Tombe Altered contractile function in heart failure Cardiovasc Res, February 1, 1998; 37(2): 367 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Hajjar, U. Schmidt, J. X. Kang, T. Matsui, and A. Rosenzweig Adenoviral Gene Transfer of Phospholamban in Isolated Rat Cardiomyocytes : Rescue Effects by Concomitant Gene Transfer of Sarcoplasmic Reticulum Ca2+-ATPase Circ. Res., August 19, 1997; 81(2): 145 - 153. [Abstract] [Full Text]
|
|
|
|
|
|
F. J. Giordano, H. He, P. McDonough, M. Meyer, M. R. Sayen, and W. H. Dillmann Adenovirus-Mediated Gene Transfer Reconstitutes Depressed Sarcoplasmic Reticulum Ca2+-ATPase Levels and Shortens Prolonged Cardiac Myocyte Ca2+ Transients Circulation, July 15, 1997; 96(2): 400 - 403. [Abstract] [Full Text]
|
|
|
|
|
|
Z. B. Kang, Y. Ge, Z. Chen, J. Cluette-Brown, M. Laposata, A. Leaf, and J. X. Kang Adenoviral gene transfer of Caenorhabditis elegansn-3 fatty acid desaturase optimizes fatty acid composition in mammalian cells PNAS, March 27, 2001; 98(7): 4050 - 4054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jane Lalli, J. Yong, V. Prasad, K. Hashimoto, D. Plank, G. J. Babu, D. Kirkpatrick, R. A. Walsh, M. Sussman, A. Yatani, et al. Sarcoplasmic Reticulum Ca2+ ATPase (SERCA) 1a Structurally Substitutes for SERCA2a in the Cardiac Sarcoplasmic Reticulum and Increases Cardiac Ca2+ Handling Capacity Circ. Res., July 20, 2001; 89(2): 160 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. DAVIA, R. J. HAJJAR, C. M. N. TERRACCIANO, N. S. KENT, H. K. RANU, P. O'GARA, A. ROSENZWEIG, and S. E. HARDING Functional alterations in adult rat myocytes after overexpression of phospholamban with use of adenovirus Physiol Genomics, August 31, 1999; 1(2): 41 - 50. [Abstract] [Full Text] [PDF]
|
|