Skip to main content
Journal cover image

Ex vivo adenovirus-mediated gene transfer to the adult rat heart.

Publication ,  Journal Article
Kypson, AP; Peppel, K; Akhter, SA; Lilly, RE; Glower, DD; Lefkowitz, RJ; Koch, WJ
Published in: J Thorac Cardiovasc Surg
March 1998

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 beta2-adrenergic receptor in a rat heterotopic heart transplant model. METHODS: Donor hearts were flushed with 10(12) 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 beta2-adrenergic receptor underwent radioligand binding assays and immunohistochemistry with the use of an antibody specific for the human beta2-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 beta2-adrenergic receptor densities (fmol/mg membrane protein) for hearts that received the beta2-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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Thorac Cardiovasc Surg

DOI

ISSN

0022-5223

Publication Date

March 1998

Volume

115

Issue

3

Start / End Page

623 / 630

Location

United States

Related Subject Headings

  • beta-Galactosidase
  • Transplantation, Heterotopic
  • Respiratory System
  • Receptors, Adrenergic, beta-2
  • Rats, Inbred Strains
  • Rats
  • Myocardium
  • Male
  • Luciferases
  • Lac Operon
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kypson, A. P., Peppel, K., Akhter, S. A., Lilly, R. E., Glower, D. D., Lefkowitz, R. J., & Koch, W. J. (1998). Ex vivo adenovirus-mediated gene transfer to the adult rat heart. J Thorac Cardiovasc Surg, 115(3), 623–630. https://doi.org/10.1016/S0022-5223(98)70327-7
Kypson, A. P., K. Peppel, S. A. Akhter, R. E. Lilly, D. D. Glower, R. J. Lefkowitz, and W. J. Koch. “Ex vivo adenovirus-mediated gene transfer to the adult rat heart.J Thorac Cardiovasc Surg 115, no. 3 (March 1998): 623–30. https://doi.org/10.1016/S0022-5223(98)70327-7.
Kypson AP, Peppel K, Akhter SA, Lilly RE, Glower DD, Lefkowitz RJ, et al. Ex vivo adenovirus-mediated gene transfer to the adult rat heart. J Thorac Cardiovasc Surg. 1998 Mar;115(3):623–30.
Kypson, A. P., et al. “Ex vivo adenovirus-mediated gene transfer to the adult rat heart.J Thorac Cardiovasc Surg, vol. 115, no. 3, Mar. 1998, pp. 623–30. Pubmed, doi:10.1016/S0022-5223(98)70327-7.
Kypson AP, Peppel K, Akhter SA, Lilly RE, Glower DD, Lefkowitz RJ, Koch WJ. Ex vivo adenovirus-mediated gene transfer to the adult rat heart. J Thorac Cardiovasc Surg. 1998 Mar;115(3):623–630.
Journal cover image

Published In

J Thorac Cardiovasc Surg

DOI

ISSN

0022-5223

Publication Date

March 1998

Volume

115

Issue

3

Start / End Page

623 / 630

Location

United States

Related Subject Headings

  • beta-Galactosidase
  • Transplantation, Heterotopic
  • Respiratory System
  • Receptors, Adrenergic, beta-2
  • Rats, Inbred Strains
  • Rats
  • Myocardium
  • Male
  • Luciferases
  • Lac Operon