Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts.

Harada, Kazumasa; Grossman, William; Friedman, Menahem; Edelman, Elazer R.; Prasad, Pottumarthi V.; Keighley, Craig S.; Manning, W. J.; Sellke, Frank W.; Simons, Michael

doi:10.1172/jci117378

Cited by 285 publications

(148 citation statements)

References 47 publications

(49 reference statements)

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“…Recent studies have demonstrated the therapeutic potential of administering FGF-2 to augment revascularization of the ischemic limb or myocardium [1,12,18,301, FGF-2 administered by repeat intramuscular injection or intra-arterial infusion has been shown to substantially increase collateral development in the ischemic area or improve the symptoms. Therefore, it is reasonable to suppose that FGF-2 could enhance angiogenesis in necrotic or avascular bone as well.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Acceleration of surgical angiogenesis in necrotic bone with a single injection of fibroblast growth factor‐2 (FGF‐2)

Nakamae¹,

Sunagawa²,

Ishida³

et al. 2004

Journal Orthopaedic Research

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The aim of this study was to accelerate angiogenesis in necrotic bone by combining vascular bundle iinplantation and fibroblast growth factor-2 (FGF-2) administration.Twenty-four Japanese white rabbits were evaluated in this study. A portion of a rabbit iliac crest bone was removed as a free bone graft and frozen in liquid nitrogen to ensure complete cellular necrosis. A narrow hole was created in the bone and the graft was placed in the proximal thigh. In group 1. FGF-2 was injected into the hole at a single dose of 100 pg. and the saphenous artery and its venae comitantes were passed through the hole of the bone. In group 2. injection of saline into the hole and the vascular bundle implantation was used as a control. Neovascularization around the vessel was evaluated at weeks I and 2 after surgery.Neovascularization was observed along the implanted vascular bundle in both groups. At both 1 and 2 weeks after surgery, the vessel density of group I was significantly higher than that of group 2. The average length of newly formed vessels of group 1 was also significantly longer than that of group 2 a t both I and 2 wceks after surgery. Both the vessel density and length were greater in week 2 animals than week I .A local single injection of FGF-2 improved surgical angiogenesis in necrotic bone in this study. As FGF-2 is recognized as a potent mitogen for a variety of mescnchymal cells. the combination ol'vascular bundle implantation and FGF-2 administration may contribute to the treatment of ischemic osteonecrosis.

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Section: Discussionmentioning

confidence: 99%

“…Recent studies have demonstrated the therapeutic potential of administering the FGF-2 to augment revascularization of the ischemic limb [l,l8] or myocardium [12,30]. In addition, FGF-2 is recognized as a potent mitogen for a variety of mesenchyrnal cells [11,22].…”

Section: € -T I I D Uddrcs\mentioning

confidence: 99%

Acceleration of surgical angiogenesis in necrotic bone with a single injection of fibroblast growth factor‐2 (FGF‐2)

Nakamae¹,

Sunagawa²,

Ishida³

et al. 2004

Journal Orthopaedic Research

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“…Recently, therapeutic angiogenesis that is based on exogenous administration of angiogenic growth factors has emerged as a promising strategy for the treatment of tissue ischemia (Lee et al, 2000b;Kim et al, 2004). The potential of therapeutic angiogenesis has been validated in various animal models of limb or myocardial ischemia and recently in patients treated with VEGF and bFGF Harada et al, 1994;Kim et al, 1994;Unger et al, 1994;Lazarous et al, 1996;Koh et al, 2002;Yamamoto et al, 2003;Hughes et al, 2004). Gene transfer can be an effective means to provide localized delivery of a high concentration of angiogenic growth factors to the ischemic tissue.…”

Section: Introductionmentioning

confidence: 99%

Cardiac expression profiles of the naked DNA vectors encoding vascular endothelial growth factor and basic fibroblast growth factor

Lee

Byun²,

Kim³

et al. 2005

Exp Mol Med

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We investigated expression profiles and biological effects of the naked DNA vectors in the heart. To this end, naked DNA vector was injected into the apex of the beating rat heart after thorocotomy. When the expression of LacZ reporter was examined by reverse transcription-PCR and histochemical staining for β-galactosidase, LacZ expression was detected only in the heart, suggesting limited dissemination of the injected vector in vivo. Even within the heart, LacZ expression was limited to the injection area (apex). Similar observations were made with other transgenes such as VEGF and basic fibroblast growth factor (bFGF), where 77% and 69% of the total transgene exprssion were detected in the heart segments containing the apex.Although VEGF and bFGF expressions were detected until 2 weeks after DNA injection, the highest levels of VEGF and bFGF were observed on day 5 and day 1, respectively. The optimal doses of the vectors were 10 µg and 25 µg for the VEGF and bFGF vectors, respectively. Interestingly, injection of bFGF vector led to 50% increase in the level of endogenous murine VEGF expression. Consistent with this finding, the number of vessels that stained positive for α-smooth muscle actin was increased in the bFGF vector-injected heart. These results suggest that simple injection of naked DNA vector may be sufficient to induce significant angiogenesis in the myocardium and that naked DNA gene therapy may be a feasible approach for the treatment of ischemic heart disease.

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“…The growth factors that have been investigated for new blood vessel formations are the vascular endothelial growth factors (VEGF) (5-7), fibroblast growth factors (8,9), and the angiopoietins (10). One of the most widely studied vascular growth factors is VEGF, a homodimeric heparin-binding glycoprotein of [34][35][36][37][38][39][40][41][42][43][44][45][46].…”

mentioning

confidence: 99%

“…VEGF injected intravenously has been shown to improve myocardial blood flow, but it also results in hypotension as a side effect (17). Alternatively, VEGF and fibroblast growth factor have been injected directly into the coronary arteries (6,8,9). The angiogenic effect appears to be transient, because most of the angiogenic factors are not retained in the heart.…”

mentioning

confidence: 99%

Adeno-associated viral vector-mediated vascular endothelial growth factor gene transfer induces neovascular formation in ischemic heart

Kan

2000

Proc. Natl. Acad. Sci. U.S.A.

147

103

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Vascular endothelial growth factor (VEGF) plays important roles in physiological and pathological angiogenesis. Recent studies have demonstrated that direct injection of VEGF protein, plasmid DNA, or an adenoviral vector encoding the VEGF gene into ischemic myocardium or limb can induce collateral blood vessel formation and improve perfusion of the ischemic areas. However, these approaches have limitations ranging from a short-lasting effect to angioma formation. In this study, we investigated the feasibility of using adeno-associated viral (AAV) vectors to deliver VEGF genes to mouse myocardium. A cytomegalovirus promoter was used to drive genes for a human VEGF isoform, VEGF 165 , and LacZ. A mouse myocardial ischemic model was generated by ligation of the anterior descending coronary artery. Approximately 10 11 copies of the AAV-VEGF vector mixed with 10 10 copies of AAV-LacZ were injected to one site of normal myocardium and a total of 10 11 copies of AAV-VEGF were injected to multiple sites of myocardium around the ischemic region. LacZ gene expression was observed up to 3 months after the vector inoculation. After AAV-VEGF inoculation, neoangiogenesis was observed in the ischemic heart model but not in normal heart tissue. An inflammatory-cell infiltration was not observed in the AAV-VEGF- and AAV-LacZ-inoculated hearts, and angioma-like structure was not observed. These results indicated that injection of the AAV vector directly to myocardium could mediate efficient gene transfer and transgene expression and that VEGF gene delivered by AAV vector can induce angiogenesis in ischemic myocardium.

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Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts.

Cited by 285 publications

References 47 publications

Acceleration of surgical angiogenesis in necrotic bone with a single injection of fibroblast growth factor‐2 (FGF‐2)

Acceleration of surgical angiogenesis in necrotic bone with a single injection of fibroblast growth factor‐2 (FGF‐2)

Cardiac expression profiles of the naked DNA vectors encoding vascular endothelial growth factor and basic fibroblast growth factor

Adeno-associated viral vector-mediated vascular endothelial growth factor gene transfer induces neovascular formation in ischemic heart

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