Transmyocardial laser revascularization limits in vivo adenoviral-mediated gene transfer in porcine myocardium

G. Chad Hughes, Brian H. Annex, Bangliang Yin, Anne M. Pippen, Pengnian Lin, Alan P. Kypson, Kevin G. Peters, James E. Lowe, Kevin P. Landolfo

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objective: Transmyocardial laser revascularization (TMR) is emerging as a potential treatment option for patients with end-stage CAD, and adjuvant gene therapy may be helpful in further improving the results of the procedure. However, the effects of TMR on gene transfer are unknown. Methods: Swine underwent left thoracotomy. TMR was performed to create five channels at 2-cm intervals in the anterolateral free wall of the left ventricle (LV) followed by injection of 1x109 plaque-forming units (pfu) of a replication-deficient adenovirus vector carrying the reporter gene β-galactosidase (Ad.Pac β-gal). An additional five direct injections of 1x109 pfu Ad.Pac β-gal were made at 2-cm intervals in the posterolateral LV of each heart. Control animals underwent TMR alone/vehicle alone (n=3) or empty virus alone/no treatment (n=3) of the anterolateral/posterolateral LV, respectively. Results: ELISA revealed significantly greater transgene expression in the direct Ad.Pac β-gal injection versus TMR plus Ad.Pac β-gal inject regions at both 3 (n=6) (273.0±58.5 vs. 133.4+28.1 pg β-gal/g protein, P=0.02) and 7 days (n=6) (180.0+59.9 vs. 56.7+18.1 pg β-gal/g protein, P=0.02) postoperatively. At 14 days postoperatively (n=2), no transgene expression was detected in either region. No transgene expression was detected in any of the control regions at 3 days postoperatively. CD-18 staining revealed significantly greater inflammation in the TMR plus Ad.Pac β-gal and TMR alone regions as compared to Ad.Pac β-gal or vehicle (P<0.001). Conclusions: Adenoviral-mediated gene transfer in conjunction with TMR is possible, although TMR appears to limit the degree of transgene expression attained as compared to direct intramyocardial injection alone, likely due to the greater immune response observed with the former. These findings may have important implications for therapeutic strategies aimed at combining TMR with gene therapy for CAD. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)81-90
Number of pages10
JournalCardiovascular Research
Volume44
Issue number1
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Transmyocardial Laser Revascularization
Myocardium
Swine
Genes
Transgenes
Heart Ventricles
Injections
Genetic Therapy
Galactosidases
Replicon
Thoracotomy
Reporter Genes
Adenoviridae
Proteins
Therapeutics

Keywords

  • Cardiovascular surgery
  • Coronary disease
  • Gene expression
  • Gene therapy
  • Inflammation
  • Swine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Hughes, G. C., Annex, B. H., Yin, B., Pippen, A. M., Lin, P., Kypson, A. P., ... Landolfo, K. P. (1999). Transmyocardial laser revascularization limits in vivo adenoviral-mediated gene transfer in porcine myocardium. Cardiovascular Research, 44(1), 81-90. https://doi.org/10.1016/S0008-6363(99)00182-0

Transmyocardial laser revascularization limits in vivo adenoviral-mediated gene transfer in porcine myocardium. / Hughes, G. Chad; Annex, Brian H.; Yin, Bangliang; Pippen, Anne M.; Lin, Pengnian; Kypson, Alan P.; Peters, Kevin G.; Lowe, James E.; Landolfo, Kevin P.

In: Cardiovascular Research, Vol. 44, No. 1, 1999, p. 81-90.

Research output: Contribution to journalArticle

Hughes, GC, Annex, BH, Yin, B, Pippen, AM, Lin, P, Kypson, AP, Peters, KG, Lowe, JE & Landolfo, KP 1999, 'Transmyocardial laser revascularization limits in vivo adenoviral-mediated gene transfer in porcine myocardium', Cardiovascular Research, vol. 44, no. 1, pp. 81-90. https://doi.org/10.1016/S0008-6363(99)00182-0
Hughes, G. Chad ; Annex, Brian H. ; Yin, Bangliang ; Pippen, Anne M. ; Lin, Pengnian ; Kypson, Alan P. ; Peters, Kevin G. ; Lowe, James E. ; Landolfo, Kevin P. / Transmyocardial laser revascularization limits in vivo adenoviral-mediated gene transfer in porcine myocardium. In: Cardiovascular Research. 1999 ; Vol. 44, No. 1. pp. 81-90.
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abstract = "Objective: Transmyocardial laser revascularization (TMR) is emerging as a potential treatment option for patients with end-stage CAD, and adjuvant gene therapy may be helpful in further improving the results of the procedure. However, the effects of TMR on gene transfer are unknown. Methods: Swine underwent left thoracotomy. TMR was performed to create five channels at 2-cm intervals in the anterolateral free wall of the left ventricle (LV) followed by injection of 1x109 plaque-forming units (pfu) of a replication-deficient adenovirus vector carrying the reporter gene β-galactosidase (Ad.Pac β-gal). An additional five direct injections of 1x109 pfu Ad.Pac β-gal were made at 2-cm intervals in the posterolateral LV of each heart. Control animals underwent TMR alone/vehicle alone (n=3) or empty virus alone/no treatment (n=3) of the anterolateral/posterolateral LV, respectively. Results: ELISA revealed significantly greater transgene expression in the direct Ad.Pac β-gal injection versus TMR plus Ad.Pac β-gal inject regions at both 3 (n=6) (273.0±58.5 vs. 133.4+28.1 pg β-gal/g protein, P=0.02) and 7 days (n=6) (180.0+59.9 vs. 56.7+18.1 pg β-gal/g protein, P=0.02) postoperatively. At 14 days postoperatively (n=2), no transgene expression was detected in either region. No transgene expression was detected in any of the control regions at 3 days postoperatively. CD-18 staining revealed significantly greater inflammation in the TMR plus Ad.Pac β-gal and TMR alone regions as compared to Ad.Pac β-gal or vehicle (P<0.001). Conclusions: Adenoviral-mediated gene transfer in conjunction with TMR is possible, although TMR appears to limit the degree of transgene expression attained as compared to direct intramyocardial injection alone, likely due to the greater immune response observed with the former. These findings may have important implications for therapeutic strategies aimed at combining TMR with gene therapy for CAD. Copyright (C) 1999 Elsevier Science B.V.",
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T1 - Transmyocardial laser revascularization limits in vivo adenoviral-mediated gene transfer in porcine myocardium

AU - Hughes, G. Chad

AU - Annex, Brian H.

AU - Yin, Bangliang

AU - Pippen, Anne M.

AU - Lin, Pengnian

AU - Kypson, Alan P.

AU - Peters, Kevin G.

AU - Lowe, James E.

AU - Landolfo, Kevin P.

PY - 1999

Y1 - 1999

N2 - Objective: Transmyocardial laser revascularization (TMR) is emerging as a potential treatment option for patients with end-stage CAD, and adjuvant gene therapy may be helpful in further improving the results of the procedure. However, the effects of TMR on gene transfer are unknown. Methods: Swine underwent left thoracotomy. TMR was performed to create five channels at 2-cm intervals in the anterolateral free wall of the left ventricle (LV) followed by injection of 1x109 plaque-forming units (pfu) of a replication-deficient adenovirus vector carrying the reporter gene β-galactosidase (Ad.Pac β-gal). An additional five direct injections of 1x109 pfu Ad.Pac β-gal were made at 2-cm intervals in the posterolateral LV of each heart. Control animals underwent TMR alone/vehicle alone (n=3) or empty virus alone/no treatment (n=3) of the anterolateral/posterolateral LV, respectively. Results: ELISA revealed significantly greater transgene expression in the direct Ad.Pac β-gal injection versus TMR plus Ad.Pac β-gal inject regions at both 3 (n=6) (273.0±58.5 vs. 133.4+28.1 pg β-gal/g protein, P=0.02) and 7 days (n=6) (180.0+59.9 vs. 56.7+18.1 pg β-gal/g protein, P=0.02) postoperatively. At 14 days postoperatively (n=2), no transgene expression was detected in either region. No transgene expression was detected in any of the control regions at 3 days postoperatively. CD-18 staining revealed significantly greater inflammation in the TMR plus Ad.Pac β-gal and TMR alone regions as compared to Ad.Pac β-gal or vehicle (P<0.001). Conclusions: Adenoviral-mediated gene transfer in conjunction with TMR is possible, although TMR appears to limit the degree of transgene expression attained as compared to direct intramyocardial injection alone, likely due to the greater immune response observed with the former. These findings may have important implications for therapeutic strategies aimed at combining TMR with gene therapy for CAD. Copyright (C) 1999 Elsevier Science B.V.

AB - Objective: Transmyocardial laser revascularization (TMR) is emerging as a potential treatment option for patients with end-stage CAD, and adjuvant gene therapy may be helpful in further improving the results of the procedure. However, the effects of TMR on gene transfer are unknown. Methods: Swine underwent left thoracotomy. TMR was performed to create five channels at 2-cm intervals in the anterolateral free wall of the left ventricle (LV) followed by injection of 1x109 plaque-forming units (pfu) of a replication-deficient adenovirus vector carrying the reporter gene β-galactosidase (Ad.Pac β-gal). An additional five direct injections of 1x109 pfu Ad.Pac β-gal were made at 2-cm intervals in the posterolateral LV of each heart. Control animals underwent TMR alone/vehicle alone (n=3) or empty virus alone/no treatment (n=3) of the anterolateral/posterolateral LV, respectively. Results: ELISA revealed significantly greater transgene expression in the direct Ad.Pac β-gal injection versus TMR plus Ad.Pac β-gal inject regions at both 3 (n=6) (273.0±58.5 vs. 133.4+28.1 pg β-gal/g protein, P=0.02) and 7 days (n=6) (180.0+59.9 vs. 56.7+18.1 pg β-gal/g protein, P=0.02) postoperatively. At 14 days postoperatively (n=2), no transgene expression was detected in either region. No transgene expression was detected in any of the control regions at 3 days postoperatively. CD-18 staining revealed significantly greater inflammation in the TMR plus Ad.Pac β-gal and TMR alone regions as compared to Ad.Pac β-gal or vehicle (P<0.001). Conclusions: Adenoviral-mediated gene transfer in conjunction with TMR is possible, although TMR appears to limit the degree of transgene expression attained as compared to direct intramyocardial injection alone, likely due to the greater immune response observed with the former. These findings may have important implications for therapeutic strategies aimed at combining TMR with gene therapy for CAD. Copyright (C) 1999 Elsevier Science B.V.

KW - Cardiovascular surgery

KW - Coronary disease

KW - Gene expression

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KW - Inflammation

KW - Swine

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