Adenoviral-mediated transfer of vascular endothelial growth factor 121 cDNA enhances myocardial perfusion and exercise performance in the nonischemic state

Paul Schalch, G. Farah Rahman, Gerald Patejunas, Robert A. Goldschmidt, Jo Ann Carbray, Mauricio A. Retuerto, David Kim, Karyn Esser, Ronald Crystal, Todd K. Rosengart

Research output: Contribution to journalArticle

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Abstract

Background: Angiogenic gene therapy has been demonstrated to enhance perfusion to ischemic tissues, but it is unknown whether the administration of angiogenic growth factors will increase blood flow to nonischemic tissues. This study investigates whether enhanced myocardial perfusion can be mediated by adenovirus-mediated transfer of vascular endothelial growth factor 121 cDNA to nonischemic myocardium. Methods: New Zealand White rabbits received adenovirus (5 × 1010 particle units) encoding for vascular endothelial growth factor 121 (n = 14) or a control vector without a transgene (n = 13) or saline solution (n = 9) via direct myocardial injection. Fluorescent microsphere perfusion studies and histologic analyses were performed 4 weeks later. In a parallel study, exercise treadmill testing was performed to assess the functional effects of this therapy in Sprague-Dawley rats. Results: Microsphere assessment of myocardial perfusion in rabbits 4 weeks after adenovirus-encoding vascular endothelial growth factor administration was greater than that for rats injected with control vector without a transgene or saline solution (3.2 ± 0.5 vs 2.7 ± 0.7 and 2.4 ± 0.4, respectively; P < .03). The endothelial cell count per high power field was increased in animals injected with adenovirus-encoding vascular endothelial growth factor versus animals injected with control vector without a transgene or saline solution (147 ± 27 vs 123 ± 14 and 125 ± 16 cells, respectively), although this did not reach statistical significance (P = .12). Rats treated with adenovirus-encoding vascular endothelial growth factor also demonstrated prolonged exercise tolerance compared with rats injected with control vector without a transgene or saline solution (exhaustion time: 26 ± 5 minutes vs 19 ± 2 minutes and 20 ± 3 minutes, respectively; P = .006). Conclusions: Adenovirus encoding-mediated transfer of vascular endothelial growth factor 121 induces an enhancement in regional perfusion in nonischemic myocardium that corresponds to changes in exercise tolerance. Adenovirus-encoding vascular endothelial growth factor therapy may be useful for inducing angiogenesis in the nonischemic state, such as for prophylactic therapy of early coronary artery disease.

Original languageEnglish
Pages (from-to)535-540
Number of pages6
JournalJournal of Thoracic and Cardiovascular Surgery
Volume127
Issue number2
DOIs
Publication statusPublished - 1 Jan 2004
Externally publishedYes

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Adenoviridae
Vascular Endothelial Growth Factor A
Complementary DNA
Perfusion
Transgenes
Sodium Chloride
Exercise Tolerance
Microspheres
Myocardium
Rabbits
Angiogenesis Inducing Agents
Genetic Therapy
Sprague Dawley Rats
Coronary Artery Disease
Intercellular Signaling Peptides and Proteins
Therapeutics
Endothelial Cells
Cell Count
Injections

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Adenoviral-mediated transfer of vascular endothelial growth factor 121 cDNA enhances myocardial perfusion and exercise performance in the nonischemic state. / Schalch, Paul; Rahman, G. Farah; Patejunas, Gerald; Goldschmidt, Robert A.; Carbray, Jo Ann; Retuerto, Mauricio A.; Kim, David; Esser, Karyn; Crystal, Ronald; Rosengart, Todd K.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 127, No. 2, 01.01.2004, p. 535-540.

Research output: Contribution to journalArticle

Schalch, Paul ; Rahman, G. Farah ; Patejunas, Gerald ; Goldschmidt, Robert A. ; Carbray, Jo Ann ; Retuerto, Mauricio A. ; Kim, David ; Esser, Karyn ; Crystal, Ronald ; Rosengart, Todd K. / Adenoviral-mediated transfer of vascular endothelial growth factor 121 cDNA enhances myocardial perfusion and exercise performance in the nonischemic state. In: Journal of Thoracic and Cardiovascular Surgery. 2004 ; Vol. 127, No. 2. pp. 535-540.
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abstract = "Background: Angiogenic gene therapy has been demonstrated to enhance perfusion to ischemic tissues, but it is unknown whether the administration of angiogenic growth factors will increase blood flow to nonischemic tissues. This study investigates whether enhanced myocardial perfusion can be mediated by adenovirus-mediated transfer of vascular endothelial growth factor 121 cDNA to nonischemic myocardium. Methods: New Zealand White rabbits received adenovirus (5 × 1010 particle units) encoding for vascular endothelial growth factor 121 (n = 14) or a control vector without a transgene (n = 13) or saline solution (n = 9) via direct myocardial injection. Fluorescent microsphere perfusion studies and histologic analyses were performed 4 weeks later. In a parallel study, exercise treadmill testing was performed to assess the functional effects of this therapy in Sprague-Dawley rats. Results: Microsphere assessment of myocardial perfusion in rabbits 4 weeks after adenovirus-encoding vascular endothelial growth factor administration was greater than that for rats injected with control vector without a transgene or saline solution (3.2 ± 0.5 vs 2.7 ± 0.7 and 2.4 ± 0.4, respectively; P < .03). The endothelial cell count per high power field was increased in animals injected with adenovirus-encoding vascular endothelial growth factor versus animals injected with control vector without a transgene or saline solution (147 ± 27 vs 123 ± 14 and 125 ± 16 cells, respectively), although this did not reach statistical significance (P = .12). Rats treated with adenovirus-encoding vascular endothelial growth factor also demonstrated prolonged exercise tolerance compared with rats injected with control vector without a transgene or saline solution (exhaustion time: 26 ± 5 minutes vs 19 ± 2 minutes and 20 ± 3 minutes, respectively; P = .006). Conclusions: Adenovirus encoding-mediated transfer of vascular endothelial growth factor 121 induces an enhancement in regional perfusion in nonischemic myocardium that corresponds to changes in exercise tolerance. Adenovirus-encoding vascular endothelial growth factor therapy may be useful for inducing angiogenesis in the nonischemic state, such as for prophylactic therapy of early coronary artery disease.",
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AU - Rahman, G. Farah

AU - Patejunas, Gerald

AU - Goldschmidt, Robert A.

AU - Carbray, Jo Ann

AU - Retuerto, Mauricio A.

AU - Kim, David

AU - Esser, Karyn

AU - Crystal, Ronald

AU - Rosengart, Todd K.

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AB - Background: Angiogenic gene therapy has been demonstrated to enhance perfusion to ischemic tissues, but it is unknown whether the administration of angiogenic growth factors will increase blood flow to nonischemic tissues. This study investigates whether enhanced myocardial perfusion can be mediated by adenovirus-mediated transfer of vascular endothelial growth factor 121 cDNA to nonischemic myocardium. Methods: New Zealand White rabbits received adenovirus (5 × 1010 particle units) encoding for vascular endothelial growth factor 121 (n = 14) or a control vector without a transgene (n = 13) or saline solution (n = 9) via direct myocardial injection. Fluorescent microsphere perfusion studies and histologic analyses were performed 4 weeks later. In a parallel study, exercise treadmill testing was performed to assess the functional effects of this therapy in Sprague-Dawley rats. Results: Microsphere assessment of myocardial perfusion in rabbits 4 weeks after adenovirus-encoding vascular endothelial growth factor administration was greater than that for rats injected with control vector without a transgene or saline solution (3.2 ± 0.5 vs 2.7 ± 0.7 and 2.4 ± 0.4, respectively; P < .03). The endothelial cell count per high power field was increased in animals injected with adenovirus-encoding vascular endothelial growth factor versus animals injected with control vector without a transgene or saline solution (147 ± 27 vs 123 ± 14 and 125 ± 16 cells, respectively), although this did not reach statistical significance (P = .12). Rats treated with adenovirus-encoding vascular endothelial growth factor also demonstrated prolonged exercise tolerance compared with rats injected with control vector without a transgene or saline solution (exhaustion time: 26 ± 5 minutes vs 19 ± 2 minutes and 20 ± 3 minutes, respectively; P = .006). Conclusions: Adenovirus encoding-mediated transfer of vascular endothelial growth factor 121 induces an enhancement in regional perfusion in nonischemic myocardium that corresponds to changes in exercise tolerance. Adenovirus-encoding vascular endothelial growth factor therapy may be useful for inducing angiogenesis in the nonischemic state, such as for prophylactic therapy of early coronary artery disease.

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