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Adenovirus-mediated genetic manipulation of the myocardial beta-adrenergic signaling system in transplanted hearts.

Publication ,  Journal Article
Shah, AS; White, DC; Tai, O; Hata, JA; Wilson, KH; Pippen, A; Kypson, AP; Glower, DD; Lefkowitz, RJ; Koch, WJ
Published in: J Thorac Cardiovasc Surg
September 2000

OBJECTIVES: Ex vivo perfusion of the cardiac allograft during organ procurement is an ideal environment for adenoviral vectors with transgenes that target improving graft contractility. One such target is the beta-adrenergic receptor-signaling system, in which alterations in transgenic mice have elucidated novel means to improve the function of the heart in vivo. The purpose of the current study was to determine the functional consequences of beta-adrenergic receptor manipulation in a rabbit model of cardiac allograft transplantation. METHODS: New Zealand White rabbits weighing 3 kg served as recipients to 1-kg outbred donors. Donor hearts were arrested and harvested, and 1 of 3 adenoviral constructs was administered into the aortic root perfusing the graft. Transgenes delivered encoded either the human beta(2)-adrenergic receptor, a peptide inhibitor of beta-adrenergic receptor densensitization, or the marker transgene beta-galactosidase. RESULTS: Five days after cervical heterotopic transplantation, left ventricular performance was measured on a Langendorff apparatus. A moderate pattern of rejection was seen in all grafts. Biventricular myocyte expression of beta-galactosidase was observed, and beta(2)-adrenergic receptor density was elevated 10-fold in grafts that received adeno-beta(2)-adrenergic receptor. Left ventricular systolic and diastolic performance was significantly increased in grafts transfected with either adeno-beta(2)-adrenergic receptor or adeno-beta-adrenergic receptor densensitization compared with control grafts that received adeno-beta-galactosidase. CONCLUSIONS: Ex vivo adenovirus-mediated gene transfer is feasible in a rabbit allograft model and, more important, genetic manipulation of beta-adrenergic receptor signaling either by increasing beta(2)-adrenergic receptor density or blocking endogenous receptor desensitization improves graft function acutely in this allograft model.

Duke Scholars

Published In

J Thorac Cardiovasc Surg

DOI

ISSN

0022-5223

Publication Date

September 2000

Volume

120

Issue

3

Start / End Page

581 / 588

Location

United States

Related Subject Headings

  • beta-Galactosidase
  • Ventricular Function, Left
  • Transplantation, Homologous
  • Transgenes
  • Respiratory System
  • Receptors, Adrenergic, beta
  • Rabbits
  • Myocardial Contraction
  • Male
  • Immunoblotting
 

Citation

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ICMJE
MLA
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Shah, A. S., White, D. C., Tai, O., Hata, J. A., Wilson, K. H., Pippen, A., … Koch, W. J. (2000). Adenovirus-mediated genetic manipulation of the myocardial beta-adrenergic signaling system in transplanted hearts. J Thorac Cardiovasc Surg, 120(3), 581–588. https://doi.org/10.1067/mtc.2000.107519
Shah, A. S., 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 120, no. 3 (September 2000): 581–88. https://doi.org/10.1067/mtc.2000.107519.
Shah AS, White DC, Tai O, Hata JA, Wilson KH, Pippen A, et al. Adenovirus-mediated genetic manipulation of the myocardial beta-adrenergic signaling system in transplanted hearts. J Thorac Cardiovasc Surg. 2000 Sep;120(3):581–8.
Shah, A. S., et al. “Adenovirus-mediated genetic manipulation of the myocardial beta-adrenergic signaling system in transplanted hearts.J Thorac Cardiovasc Surg, vol. 120, no. 3, Sept. 2000, pp. 581–88. Pubmed, doi:10.1067/mtc.2000.107519.
Shah AS, White DC, Tai O, Hata JA, Wilson KH, Pippen A, Kypson AP, Glower DD, Lefkowitz RJ, Koch WJ. Adenovirus-mediated genetic manipulation of the myocardial beta-adrenergic signaling system in transplanted hearts. J Thorac Cardiovasc Surg. 2000 Sep;120(3):581–588.
Journal cover image

Published In

J Thorac Cardiovasc Surg

DOI

ISSN

0022-5223

Publication Date

September 2000

Volume

120

Issue

3

Start / End Page

581 / 588

Location

United States

Related Subject Headings

  • beta-Galactosidase
  • Ventricular Function, Left
  • Transplantation, Homologous
  • Transgenes
  • Respiratory System
  • Receptors, Adrenergic, beta
  • Rabbits
  • Myocardial Contraction
  • Male
  • Immunoblotting