HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Alan P. Kypson R. Eric Lilly Donald D. Glower Robert W. Anderson Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kypson, A. P. Articles by Anderson, R. W. Search for Related Content PubMed PubMed Citation Articles by Kypson, A. P. Articles by Anderson, R. W.

J Thorac Cardiovasc Surg 1998;115:623-630
© 1998 Mosby, Inc.

CARDIAC AND PULMONARY REPLACEMENT

Ex Vivo Adenovirus-Mediated Gene Transfer To The Adult Rat Heart

Sponsor:

Robert W. Anderson, MD^a

From the Departments of Surgery^a and Medicine and Biochemistry,^b Duke University Medical Center, and Howard Hughes Medical Institute,^c Durham, N.C.

Read at the Seventy-seventh Annual Meeting of The American Associationfor Thoracic Surgery, Washington, D.C., May 4-7, 1997.

Received for publication May 7, 1997; revisions requested July 15, 1997; revisions received Sept. 29, 1997; accepted for publication Sept. 30, 1997 Address for reprints: Alan P. Kypson, MD, Box 3490, DukeUniversity Medical Center, Durham, NC 27710.

Abstract

Objective: The ability to transfer genes to adult myocardium may have therapeutic implications for cardiac transplantation. We investigated the feasibility of adenovirus-mediated transfer of marker genes LacZ and Luciferase, as well as the potentially therapeutic gene of the human ß₂-adrenergic receptor in a rat heterotopic heart transplant model.
Methods: Donor hearts were flushed with 10¹² total viral particles of one of three transgenes. Hearts were harvested at various time points after transplantation. LacZ-treated hearts were assessed by histologic staining and Luciferase-treated hearts were assayed for specific luminescence activity. Hearts treated with ß₂-adrenergic receptor underwent radioligand binding assays and immunohistochemistry with the use of an antibody specific for the human ß₂-adrenergic receptor.
Results: LacZ hearts revealed diffuse myocyte staining as opposed to none within controls at 5 days. Luciferase hearts demonstrated a mean activity of 970,000 ± 220,000 arbitrary light units versus 500 ± 200 for the controls (p = 0.001). Total ß₂-adrenergic receptor densities (fmol/mg membrane protein) for hearts that received the ß₂-adrenergic receptor transgene at 3, 5, 7, 10, and 14 days after infection were as follows: right ventricle, 488.5 ± 126.8, 519.4 ± 81.8,* 477.1 ± 51.8,* 183.0 ± 6.5,* and 82.7 ± 19.1; left ventricle, 511.0 ± 167.6, 1206.4 ± 321.8,* 525.3 ± 188.7, 183.5 ± 18.6,* and 75.9 ± 15.2 (*p  < 0.05 vs control value of 75.6 ± 6.4). Immunohistochemical analysis revealed diffuse staining of varying intensity within myocardial sarcolemmal membranes.
Conclusions: We conclude that global overexpression of different transgenes is possible during cardiac transplantation and, ultimately, adenovirus-mediated gene transfer may provide a unique opportunity for genetic manipulation of the donor organ, potentially enhancing its function.

This article has been cited by other articles:

				A. Nakamura, R. Niimi, and Y. Yanagawa Protection from sepsis-induced acute renal failure by adenoviral-mediated gene transfer of {beta}2-adrenoceptor Nephrol. Dial. Transplant., November 3, 2009; (2009) gfp561v1. [Abstract] [Full Text] [PDF]

				P. K. Pandalai, J. M. Lyons, J. Y. Duffy, K. M. McLean, C. J. Wagner, W. H. Merrill, J. M. Pearl, and S. A. Akhter Role of the {beta}-adrenergic receptor kinase in myocardial dysfunction after brain death J. Thorac. Cardiovasc. Surg., October 1, 2005; 130(4): 1183 - 1189. [Abstract] [Full Text] [PDF]

				X. Deng, S. Szabo, T. Khomenko, M. R. Jadus, and M. Yoshida Gene Therapy with Adenoviral Plasmids or Naked DNA of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor Accelerates Healing of Duodenal Ulcer in Rats J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 982 - 988. [Abstract] [Full Text] [PDF]

				A. Sasse, Z. Ding, M. Wallich, A. Godecke, and J. Schrader Vascular transfer of adenovirus is augmented by nitric oxide in the rat heart Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1362 - H1368. [Abstract] [Full Text] [PDF]

				A. Nakamura, A. Imaizumi, Y. Yanagawa, T. Kohsaka, and E. J. Johns {beta}2-Adrenoceptor Activation Attenuates Endotoxin-Induced Acute Renal Failure J. Am. Soc. Nephrol., February 1, 2004; 15(2): 316 - 325. [Abstract] [Full Text] [PDF]

				H. T. Tevaearai, A. D. Eckhart, K. F. Shotwell, K. Wilson, and W. J. Koch Ventricular Dysfunction After Cardioplegic Arrest Is Improved After Myocardial Gene Transfer of a {beta}-Adrenergic Receptor Kinase Inhibitor Circulation, October 23, 2001; 104(17): 2069 - 2074. [Abstract] [Full Text] [PDF]

				M. J. Davidson, J. M. Jones, S. M. Emani, K. H. Wilson, J. Jaggers, W. J. Koch, and C. A. Milano Cardiac Gene Delivery With Cardiopulmonary Bypass Circulation, July 10, 2001; 104(2): 131 - 133. [Abstract] [Full Text] [PDF]

				A. S. Shah, D. C. White, O. Tai, J. A. Hata, K. H. Wilson, A. Pippen, A. P. Kypson, D. D. Glower, R. J. Lefkowitz, and W. J. Koch Adenovirus-mediated genetic manipulation of the myocardial {beta}-adrenergic signaling system in transplanted hearts J. Thorac. Cardiovasc. Surg., September 1, 2000; 120(3): 581 - 588. [Abstract] [Full Text] [PDF]

				S. E. Lehnart, P. M. L. Janssen, W. M. Franz, J. K. Donahue, J. H. Lawrence, E. Marban, J. Prestle, and G. Hasenfuss Preservation of myocardial function after adenoviral gene transfer in isolated myocardium Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H986 - H991. [Abstract] [Full Text] [PDF]

				C. Pellegrini, A. Jeppsson, C. B. Taner, T. O’Brien, V. M. Miller, H. D. Tazelaar, and C. G. A. McGregor HIGHLY EFFICIENT EX VIVO GENE TRANSFER TO THE TRANSPLANTED HEART BY MEANS OF HYPOTHERMIC PERFUSION WITH A LOW DOSE OF ADENOVIRAL VECTOR J. Thorac. Cardiovasc. Surg., March 1, 2000; 119(3): 493 - 500. [Abstract] [Full Text] [PDF]

				A. S. Shah, R. E. Lilly, A. P. Kypson, O. Tai, J. A. Hata, A. Pippen, S. C. Silvestry, R. J. Lefkowitz, D. D. Glower, and W. J. Koch Intracoronary Adenovirus-Mediated Delivery and Overexpression of the {beta}2-Adrenergic Receptor in the Heart : Prospects for Molecular Ventricular Assistance Circulation, February 1, 2000; 101(4): 408 - 414. [Abstract] [Full Text] [PDF]