Enhanced vasorelaxation by overexpression of β2-adrenergic receptors in large arteries

Mohamed A. Gaballa, Karsten Peppel, Robert J. Lefkowitz, Maria Aguirre, Paul C. Dolber, Gregory D. Pennock, Walter J. Koch, Steven Goldman

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

This study was designed to determine if adenoviral-mediated delivery of a transgene encoding the β2-adrenergic receptor (β2-AR) to the carotid arterial wall could result in alterations in in vivo vascular function. De-endothelialized rat carotid arteries were infused in vivo with 0.1 mg/ml elastase and adenovirus [6 x 109 plaque forming units (PFU)] containing either the marker gene β-galactosidase (Adeno-β-gal), DNA encoding the human β2-AR (Adeno-β2-AR), or no transgene. This low concentration of elastase increased the water permeability (5.2 ± 0.6 v 1.9 ± 0.4 x 10-8 cm/s/mmHg, n = 4, P < 0.0001) without affecting either the vasomotor responsiveness or the morphology of the arterial wall. A transfection efficiency of 73% was achieved with Adeno-β-gal (n = 3). β-gal expression was associated with infrequent appearance of T and B lymphocytes, or neutrophil infiltration. Five days after infection with Adeno-β2-AR, the total β-AR density increased six-fold (67.8 ± 3.4 v 397.0 ± 155.5 fmol/mg protein, n = 5, P < 0.01); isoproterenol-induced vasorelaxation at transmural pressures from 10-110 mmHg increased (P < 0.01) compared to arteries exposed to control virus (empty adenovirus), n = 4; and isoproterenol-stimulated cAMP production was increased by 65% (n = 5). Thus, adenoviral-mediated delivery of β2-ARs into large artery walls results in enhanced β-AR-mediated vasorelaxation via augmentation in cAMP levels in vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)1037-1045
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume30
Issue number5
DOIs
StatePublished - May 1998
Externally publishedYes

Fingerprint

Pancreatic Elastase
Transgenes
Isoproterenol
Adenoviridae
Vasodilation
Adrenergic Receptors
Arteries
Galactosidases
Neutrophil Infiltration
DNA
Vascular Smooth Muscle
Carotid Arteries
Smooth Muscle Myocytes
Transfection
Blood Vessels
Permeability
B-Lymphocytes
Viruses
T-Lymphocytes
Pressure

Keywords

  • β-receptors
  • Gene transfer
  • Vascular tone

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Gaballa, M. A., Peppel, K., Lefkowitz, R. J., Aguirre, M., Dolber, P. C., Pennock, G. D., ... Goldman, S. (1998). Enhanced vasorelaxation by overexpression of β2-adrenergic receptors in large arteries. Journal of Molecular and Cellular Cardiology, 30(5), 1037-1045. https://doi.org/10.1006/jmcc.1998.0668

Enhanced vasorelaxation by overexpression of β2-adrenergic receptors in large arteries. / Gaballa, Mohamed A.; Peppel, Karsten; Lefkowitz, Robert J.; Aguirre, Maria; Dolber, Paul C.; Pennock, Gregory D.; Koch, Walter J.; Goldman, Steven.

In: Journal of Molecular and Cellular Cardiology, Vol. 30, No. 5, 05.1998, p. 1037-1045.

Research output: Contribution to journalArticle

Gaballa, MA, Peppel, K, Lefkowitz, RJ, Aguirre, M, Dolber, PC, Pennock, GD, Koch, WJ & Goldman, S 1998, 'Enhanced vasorelaxation by overexpression of β2-adrenergic receptors in large arteries', Journal of Molecular and Cellular Cardiology, vol. 30, no. 5, pp. 1037-1045. https://doi.org/10.1006/jmcc.1998.0668
Gaballa, Mohamed A. ; Peppel, Karsten ; Lefkowitz, Robert J. ; Aguirre, Maria ; Dolber, Paul C. ; Pennock, Gregory D. ; Koch, Walter J. ; Goldman, Steven. / Enhanced vasorelaxation by overexpression of β2-adrenergic receptors in large arteries. In: Journal of Molecular and Cellular Cardiology. 1998 ; Vol. 30, No. 5. pp. 1037-1045.
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