Similar articles

Abstract: Objective: Angiogenic therapy is emerging as a potential strategy for the treatment of ischemic heart disease but is limited by a relatively short half-life of growth factors. Fibrin glue (FG) provides a reservoir for controlled-release of growth factors. The aim of this study was to evaluate the effects of basic fibroblast growth factor (bFGF) incorporating FG on angiogenesis and cardiac performance in a canine infarct model. Methods: Acute myocardial infarction was induced by ligation of the left anterior descending coronary artery (LAD). Group I (n=6) underwent ligation of LAD alone. In Group II, transmural channels were created in the infarct area (n=6). In Group III, non-transmural channels were created to locate FG cylinders containing bFGF (n=6). Eight weeks after operation, myocardial perfusion was assessed by single photon emission computed tomography, cardiac function by echocardiography, and vascular development by immunohistochemical staining. Results: Total vascular density and the number of large vessels (internal diameter ≥50 μm) were dramatically higher in Group III than in Groups I and II at eight weeks. Only the controlled-release group exhibited an improvement in regional myocardial perfusion associated with lower defect score. Animals in Group III presented improved cardiac regional systolic and diastolic functions as well as global systolic function in comparison with the other two groups. Conclusions: Enhanced and sustained angiogenic response can be achieved by controlled-release bFGF incorporating FG within transmyocardial laser channels, thus enabling improvement in myocardial perfusion and cardiac function.

[1]Beenken, A., Mohammadi, M., 2009. The FGF family: biology, pathophysiology and therapy. Nat. Rev. Drug Discov., 8(3):235-253.

[2]Bourdillon, P.D., Broderick, T.M., Sawada, S.G., Armstrong, W.F., Ryan, T., Dillon, J.C., Fineberg, N.S., Feigenbaum, H., 1989. Regional wall motion index for infarct and noninfarct regions after reperfusion in acute myocardial infarction: comparison with global wall motion index. J. Am. Soc. Echocardiogr., 2(6):398-407.

[3]Brown, K.J., Maynes, S.F., Bezos, A., Maguire, D.J., Ford, M.D., Parish, C.R., 1996. A novel in vitro assay for human angiogenesis. Lab. Invest., 75(4):539-555.

[4]Chawla, P.S., Keelan, M.H., Kipshidze, N., 1999. Angiogenesis for the treatment of vascular diseases. Int. Angiol., 18(3):185-192.

[5]Choi, J.S., Kim, K.B., Han, W., Kim, D.S., Park, J.S., Lee, J.J., Lee, D.S., 2006. Efficacy of therapeutic angiogenesis by intramyocardial injection of pCK-VEGF165 in pigs. Ann. Thorac. Surg., 82(2):679-686.

[6]Currie, L.J., Sharpe, J.R., Martin, R., 2001. The use of fibrin glue in skin grafts and tissue-engineered skin replacements: a review. Plast. Reconstr. Surg., 108(6):1713-1726.

[7]DeBlois, C., Cote, M.F., Doillon, C.J., 1994. Heparin-fibroblast growth factor-fibrin complex: in vitro and in vivo applications to collagen-based materials. Biomaterials, 15(9):665-672.

[8]Fasol, R., Schumacher, B., Schlaudraff, K., Hauenstein, K.H., Seitelberger, R., 1994. Experimental use of a modified fibrin glue to induce site-directed angiogenesis from the aorta to the heart. J. Thorac. Cardiovasc. Surg., 107(6):1432-1439.

[9]Germano, G., Kavanagh, P.B., Waechter, P., Areeda, J., van Kriekinge, S., Sharir, T., Lewin, H.C., Berman, D.S., 2000. A new algorithm for the quantitation of myocardial perfusion SPECT. I: technical principles and reproducibility. J. Nucl. Med., 41(4):712-719.

[10]Harada, K., Grossman, W., Friedman, M., Edelman, E.R., Prasad, P.V., Keighley, C.S., Manning, W.J., Sellke, F.W., Simons, M., 1994. Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts. J. Clin. Invest., 94(2):623-630.

[11]Heilmann, C.A., Attmann, T., von Samson, P., Gobel, H., Marme, D., Beyersdorf, F., Lutter, G., 2003. Transmyocardial laser revascularization combined with vascular endothelial growth factor 121 (VEGF121) gene therapy for chronic myocardial ischemia—do the effects really add up? Eur. J. Cardiothorac. Surg., 23(1):74-80.

[12]Henry, T.D., Annex, B.H., McKendall, G.R., Azrin, M.A., Lopez, J.J., Giordano, F.J., Shah, P.K., Willerson, J.T., Benza, R.L., Berman, D.S., et al., 2003. The VIVA trial: vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation, 107(10):1359-1365.

[13]Henry, T.D., Grines, C.L., Watkins, M.W., Dib, N., Barbeau, G., Moreadith, R., Andrasfay, T., Engler, R.L., 2007. Effects of Ad5FGF-4 in patients with angina: an analysis of pooled data from the AGENT-3 and AGENT-4 trials. J. Am. Coll. Cardiol., 50(11):1038-1046.

[14]House, S.L., Bolte, C., Zhou, M., Doetschman, T., Klevitsky, R., Newman, G., Schultz Jel, J., 2003. Cardiac-specific overexpression of fibroblast growth factor-2 protects against myocardial dysfunction and infarction in a murine model of low-flow ischemia. Circulation, 108(25):3140-3148.

[15]Hughes, G.C., Kypson, A.P., St. Louis, J.D., Annex, B.H., Coleman, R.E., DeGrado, T.R., Donovan, C.L., Lowe, J.E., Landolfo, K.P., 1999. Improved perfusion and contractile reserve after transmyocardial laser revascularization in a model of hibernating myocardium. Ann. Thorac. Surg., 67(6):1714-1720.

[16]Iwakura, A., Fujita, M., Kataoka, K., Tambara, K., Sakakibara, Y., Komeda, M., Tabata, Y., 2003. Intramyocardial sustained delivery of basic fibroblast growth factor improves angiogenesis and ventricular function in a rat infarct model. Heart Vessels, 18(2):93-99.

[17]Jeon, O., Ryu, S.H., Chung, J.H., Kim, B.S., 2005. Control of basic fibroblast growth factor release from fibrin gel with heparin and concentrations of fibrinogen and thrombin. J. Control Release, 105(3):249-259.

[18]Jiang, Z.S., Srisakuldee, W., Soulet, F., Bouche, G., Kardami, E., 2004. Non-angiogenic FGF-2 protects the ischemic heart from injury, in the presence or absence of reperfusion. Cardiovasc. Res., 62(1):154-166.

[19]Kang, S.S., Gosselin, C., Ren, D., Greisler, H.P., 1995. Selective stimulation of endothelial cell proliferation with inhibition of smooth muscle cell proliferation by fibroblast growth factor-1 plus heparin delivered from fibrin glue suspensions. Surgery, 118(2):280-287.

[20]Karacal, N., Cobanoglu, U., Ambarcioglu, O., Kutlu, N., 2007. The effect of fibrin glue on fat graft survival. J. Plast. Reconstr. Aesthet. Surg., 60(3):300-303.

[21]Kastrup, J., Jorgensen, E., Ruck, A., Tagil, K., Glogar, D., Ruzyllo, W., Botker, H.E., Dudek, D., Drvota, V., Hesse, B., et al., 2005. Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study: the Euroinject One trial. J. Am. Coll. Cardiol., 45(7):982-988.

[22]Kawasuji, M., Nagamine, H., Ikeda, M., Sakakibara, N., Takemura, H., Fujii, S., Watanabe, Y., 2000. Therapeutic angiogenesis with intramyocardial administration of basic fibroblast growth factor. Ann. Thorac. Surg., 69(4):1155-1161.

[23]Kornowski, R., Fuchs, S., Leon, M.B., Epstein, S.E., 2000a. Delivery strategies to achieve therapeutic myocardial angiogenesis. Circulation, 101(4):454-458.

[24]Kornowski, R., Baim, D.S., Moses, J.W., Hong, M.K., Laham, R.J., Fuchs, S., Hendel, R.C., Wallace, D., Cohen, D.J., Bonow, R.O., et al., 2000b. Short- and intermediate-term clinical outcomes from direct myocardial laser revascularization guided by Biosense left ventricular electromechanical mapping. Circulation, 102(10):1120-1125.

[25]Laham, R.J., Garcia, L., Baim, D.S., Post, M., Simons, M., 1999. Therapeutic angiogenesis using basic fibroblast growth factor and vascular endothelial growth factor using various delivery strategies. Curr. Interv. Cardiol. Rep., 1(3):228-233.

[26]Laham, R.J., Chronos, N.A., Pike, M., Leimbach, M.E., Udelson, J.E., Pearlman, J.D., Pettigrew, R.I., Whitehouse, M.J., Yoshizawa, C., Simons, M., 2000. Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a phase I open-label dose escalation study. J. Am. Coll. Cardiol., 36(7):2132-2139.

[27]Lopez, J.J., Edelman, E.R., Stamler, A., Hibberd, M.G., Prasad, P., Caputo, R.P., Carrozza, J.P., Douglas, P.S., Sellke, F.W., Simons, M., 1997. Basic fibroblast growth factor in a porcine model of chronic myocardial ischemia: a comparison of angiographic, echocardiographic and coronary flow parameters. J. Pharmacol. Exp. Ther., 282(1):385-390.

[28]Phelps, E.A., Garcia, A.J., 2009. Update on therapeutic vascularization strategies. Regen. Med., 4(1):65-80.

[29]Post, M.J., Laham, R., Sellke, F.W., Simons, M., 2001. Therapeutic angiogenesis in cardiology using protein formulations. Cardiovasc. Res., 49(3):522-531.

[30]Sahni, A., Odrljin, T., Francis, C.W., 1998. Binding of basic fibroblast growth factor to fibrinogen and fibrin. J. Biol. Chem., 273(13):7554-7559.

[31]Sahni, A., Khorana, A.A., Baggs, R.B., Peng, H., Francis, C.W., 2006. FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis. Blood, 107(1):126-131.

[32]Shao, Z.Q., Takaji, K., Katayama, Y., Kunitomo, R., Sakaguchi, H., Lai, Z.F., Kawasuji, M., 2006. Effects of intramyocardial administration of slow-release basic fibroblast growth factor on angiogenesis and ventricular remodeling in a rat infarct model. Circ. J., 70(4):471-477.

[33]Simons, M., Annex, B.H., Laham, R.J., Kleiman, N., Henry, T., Dauerman, H., Udelson, J.E., Gervino, E.V., Pike, M., Whitehouse, M.J., et al., 2002. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial. Circulation, 105(7):788-793.

[34]Stewart, D.J., Kutryk, M.J., Fitchett, D., Freeman, M., Camack, N., Su, Y., Della Siega, A., Bilodeau, L., Burton, J.R., Proulx, G., et al., 2009. VEGF gene therapy fails to improve perfusion of ischemic myocardium in patients with advanced coronary disease: results of the NORTHERN trial. Mol. Ther., 17(6):1109-1115.

[35]Sutton, M.G., Sharpe, N., 2000. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation, 101(25):2981-2988.

[36]Yamamoto, N., Kohmoto, T., Roethy, W., Gu, A., DeRosa, C., Rabbani, L.E., Smith, C.R., Burkhoff, D., 2000. Histologic evidence that basic fibroblast growth factor enhances the angiogenic effects of transmyocardial laser revascularization. Basic Res. Cardiol., 95(1):55-63.