Myocardial functional recovery after fibroblast growth factor 2 gene therapy as assessed by echocardiography and magnetic resonance imaging

Keith A. Horvath, John Doukas, Chia Yang J Lu, Noam Belkind, Rodney Greene, Glenn F. Pierce, David A. Fullerton

Research output: Contribution to journalArticle

Abstract

Background. Although it has been shown that gene therapy is capable of inducing neovascularization in ischemic myocardium, the functional significance of such therapeutic angiogenesis remains less certain. The purpose of this study was to investigate whether an experimental link could be made between the ability of a novel fibroblast growth factor 2 (FGF2) gene formulation to promote neovascularization, and its ability to restore myocardial function. Methods. Fibroblast growth factor 2 gene was delivered by means of an adenovirus vector formulated in a collagen-based matrix to provide localized and sustained gene activity. Using a model of chronic myocardial ischemia, animals were randomized to either treatment of the ischemic area by injections of adenovirus vector-FGF2 or no treatment. Left ventricular function was assessed by rest and dobutamine stress echocardiography as well as contrast-enhanced and cine magnetic resonance imaging scans. Studies were repeated 6 weeks after treatment. Arteriogenesis was assessed by quantifying the total arteriolar wall area present in treated areas, using anti-α-actin immunohistochemistry and subsequent morphometric analyses. Results. Echocardiographic results demonstrated a significant restoration of myocardial function in FGF2 gene-treated areas as measured by myocardial wall thickening (0.38 ± 0.08 cm pretreatment versus 0.76 ± 0.09 cm posttreatment; p <0.05). This was demonstrated by comparing the ischemic zones of FGF2 gene-treated versus control-treated animals, as well as by comparing ischemic with nonischemic zones in individual animals This functional improvement was confirmed by cine magnetic resonance imaging, in which 68% (147 of 216) of the treated segments showed improvement in wall motion and there was no change in the untreated segments. Fibroblast growth factor 2 gene treatment also enhanced arteriogenesis within the ischemic zone, as FGF2 gene-treated animals showed a 340% increase in the total arteriolar wall area present versus control-treated animals. Conclusions. The function of ischemic myocardium can be restored by a novel FGF2 gene delivery method using a gene-activated matrix. The increased arteriogenesis as a result of FGF2 gene therapy leads to restoration of this myocardial function.

Original languageEnglish (US)
Pages (from-to)481-487
Number of pages7
JournalAnnals of Thoracic Surgery
Volume74
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

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Fibroblast Growth Factor 2
Genetic Therapy
Echocardiography
Magnetic Resonance Imaging
Genes
Cine Magnetic Resonance Imaging
Adenoviridae
Myocardium
Therapeutics
Stress Echocardiography
Left Ventricular Function
Myocardial Ischemia
Actins
Collagen
Immunohistochemistry
Injections

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Myocardial functional recovery after fibroblast growth factor 2 gene therapy as assessed by echocardiography and magnetic resonance imaging. / Horvath, Keith A.; Doukas, John; Lu, Chia Yang J; Belkind, Noam; Greene, Rodney; Pierce, Glenn F.; Fullerton, David A.

In: Annals of Thoracic Surgery, Vol. 74, No. 2, 2002, p. 481-487.

Research output: Contribution to journalArticle

Horvath, Keith A. ; Doukas, John ; Lu, Chia Yang J ; Belkind, Noam ; Greene, Rodney ; Pierce, Glenn F. ; Fullerton, David A. / Myocardial functional recovery after fibroblast growth factor 2 gene therapy as assessed by echocardiography and magnetic resonance imaging. In: Annals of Thoracic Surgery. 2002 ; Vol. 74, No. 2. pp. 481-487.
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abstract = "Background. Although it has been shown that gene therapy is capable of inducing neovascularization in ischemic myocardium, the functional significance of such therapeutic angiogenesis remains less certain. The purpose of this study was to investigate whether an experimental link could be made between the ability of a novel fibroblast growth factor 2 (FGF2) gene formulation to promote neovascularization, and its ability to restore myocardial function. Methods. Fibroblast growth factor 2 gene was delivered by means of an adenovirus vector formulated in a collagen-based matrix to provide localized and sustained gene activity. Using a model of chronic myocardial ischemia, animals were randomized to either treatment of the ischemic area by injections of adenovirus vector-FGF2 or no treatment. Left ventricular function was assessed by rest and dobutamine stress echocardiography as well as contrast-enhanced and cine magnetic resonance imaging scans. Studies were repeated 6 weeks after treatment. Arteriogenesis was assessed by quantifying the total arteriolar wall area present in treated areas, using anti-α-actin immunohistochemistry and subsequent morphometric analyses. Results. Echocardiographic results demonstrated a significant restoration of myocardial function in FGF2 gene-treated areas as measured by myocardial wall thickening (0.38 ± 0.08 cm pretreatment versus 0.76 ± 0.09 cm posttreatment; p <0.05). This was demonstrated by comparing the ischemic zones of FGF2 gene-treated versus control-treated animals, as well as by comparing ischemic with nonischemic zones in individual animals This functional improvement was confirmed by cine magnetic resonance imaging, in which 68{\%} (147 of 216) of the treated segments showed improvement in wall motion and there was no change in the untreated segments. Fibroblast growth factor 2 gene treatment also enhanced arteriogenesis within the ischemic zone, as FGF2 gene-treated animals showed a 340{\%} increase in the total arteriolar wall area present versus control-treated animals. Conclusions. The function of ischemic myocardium can be restored by a novel FGF2 gene delivery method using a gene-activated matrix. The increased arteriogenesis as a result of FGF2 gene therapy leads to restoration of this myocardial function.",
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T1 - Myocardial functional recovery after fibroblast growth factor 2 gene therapy as assessed by echocardiography and magnetic resonance imaging

AU - Horvath, Keith A.

AU - Doukas, John

AU - Lu, Chia Yang J

AU - Belkind, Noam

AU - Greene, Rodney

AU - Pierce, Glenn F.

AU - Fullerton, David A.

PY - 2002

Y1 - 2002

N2 - Background. Although it has been shown that gene therapy is capable of inducing neovascularization in ischemic myocardium, the functional significance of such therapeutic angiogenesis remains less certain. The purpose of this study was to investigate whether an experimental link could be made between the ability of a novel fibroblast growth factor 2 (FGF2) gene formulation to promote neovascularization, and its ability to restore myocardial function. Methods. Fibroblast growth factor 2 gene was delivered by means of an adenovirus vector formulated in a collagen-based matrix to provide localized and sustained gene activity. Using a model of chronic myocardial ischemia, animals were randomized to either treatment of the ischemic area by injections of adenovirus vector-FGF2 or no treatment. Left ventricular function was assessed by rest and dobutamine stress echocardiography as well as contrast-enhanced and cine magnetic resonance imaging scans. Studies were repeated 6 weeks after treatment. Arteriogenesis was assessed by quantifying the total arteriolar wall area present in treated areas, using anti-α-actin immunohistochemistry and subsequent morphometric analyses. Results. Echocardiographic results demonstrated a significant restoration of myocardial function in FGF2 gene-treated areas as measured by myocardial wall thickening (0.38 ± 0.08 cm pretreatment versus 0.76 ± 0.09 cm posttreatment; p <0.05). This was demonstrated by comparing the ischemic zones of FGF2 gene-treated versus control-treated animals, as well as by comparing ischemic with nonischemic zones in individual animals This functional improvement was confirmed by cine magnetic resonance imaging, in which 68% (147 of 216) of the treated segments showed improvement in wall motion and there was no change in the untreated segments. Fibroblast growth factor 2 gene treatment also enhanced arteriogenesis within the ischemic zone, as FGF2 gene-treated animals showed a 340% increase in the total arteriolar wall area present versus control-treated animals. Conclusions. The function of ischemic myocardium can be restored by a novel FGF2 gene delivery method using a gene-activated matrix. The increased arteriogenesis as a result of FGF2 gene therapy leads to restoration of this myocardial function.

AB - Background. Although it has been shown that gene therapy is capable of inducing neovascularization in ischemic myocardium, the functional significance of such therapeutic angiogenesis remains less certain. The purpose of this study was to investigate whether an experimental link could be made between the ability of a novel fibroblast growth factor 2 (FGF2) gene formulation to promote neovascularization, and its ability to restore myocardial function. Methods. Fibroblast growth factor 2 gene was delivered by means of an adenovirus vector formulated in a collagen-based matrix to provide localized and sustained gene activity. Using a model of chronic myocardial ischemia, animals were randomized to either treatment of the ischemic area by injections of adenovirus vector-FGF2 or no treatment. Left ventricular function was assessed by rest and dobutamine stress echocardiography as well as contrast-enhanced and cine magnetic resonance imaging scans. Studies were repeated 6 weeks after treatment. Arteriogenesis was assessed by quantifying the total arteriolar wall area present in treated areas, using anti-α-actin immunohistochemistry and subsequent morphometric analyses. Results. Echocardiographic results demonstrated a significant restoration of myocardial function in FGF2 gene-treated areas as measured by myocardial wall thickening (0.38 ± 0.08 cm pretreatment versus 0.76 ± 0.09 cm posttreatment; p <0.05). This was demonstrated by comparing the ischemic zones of FGF2 gene-treated versus control-treated animals, as well as by comparing ischemic with nonischemic zones in individual animals This functional improvement was confirmed by cine magnetic resonance imaging, in which 68% (147 of 216) of the treated segments showed improvement in wall motion and there was no change in the untreated segments. Fibroblast growth factor 2 gene treatment also enhanced arteriogenesis within the ischemic zone, as FGF2 gene-treated animals showed a 340% increase in the total arteriolar wall area present versus control-treated animals. Conclusions. The function of ischemic myocardium can be restored by a novel FGF2 gene delivery method using a gene-activated matrix. The increased arteriogenesis as a result of FGF2 gene therapy leads to restoration of this myocardial function.

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