© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Therapeutic angiogenesis in cardiology using protein formulations
Angiogenesis Research Center and Cardiothoracic Surgery Division (FWS), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
* Corresponding author. Tel.:+1-617-667-3790; fax: +1-617-975-5201 mpost{at}caregroup.harvard.edu
Therapeutic angiogenesis in cardiovascular disease aims at improving myocardial function by increasing blood flow to ischemic myocardium that is not amenable to traditional forms of revascularization. Preclinical data have provided proof of the concept that angiogenic growth factors such as fibroblast growth factor 2 (FGF-2) and vascular endothelium growth factor (VEGF) may indeed improve myocardial flow and function when administered in ways that ensure prolonged tissue exposure to these short-lived molecules. Although other cytokines have been shown to enhance angiogenesis in vivo, FGF-2 and VEGF have been most widely studied and may serve as prototype proangiogenic drugs. Currently, several delivery techniques that are clinically applicable are being studied with respect to tissue distribution and retention as well as angiogenic efficacy of FGF-2 and VEGF. Although tissue distribution and retention of FGF-2 after intramyocardial injection compares favorably with other routes of administration, efficacy studies are not yet conclusive. At the same time, different protein- and gene-based formulations are being investigated. Arguments for and against protein and gene therapy are presented, showing that protein-based therapy seems to have advantages over gene therapy at the present time, although continuous efforts should be made to increase the tissue exposure time after a single administration of protein. While delivery systems and growth factor formulations are being improved, double-blind, placebo-controlled trials designed with existing animal data in mind, are needed to firmly establish the utility of therapeutic angiogenesis in cardiovascular disease.
KEYWORDS Angiogenisis; Coronory disease
1 Angiogenesis Research Center, Beth Israel Deaconess Medical Center, Room SL 423 330 Brookline Ave, Boston, MA, USA 02215.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Zisa, A. Shabbir, M. Mastri, G. Suzuki, and T. Lee Intramuscular VEGF repairs the failing heart: role of host-derived growth factors and mobilization of progenitor cells Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1503 - R1515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zimpfer, S. Aharinejad, J. Holfeld, A. Thomas, J. Dumfarth, R. Rosenhek, M. Czerny, W. Schaden, M. Gmeiner, E. Wolner, et al. Direct epicardial shock wave therapy improves ventricular function and induces angiogenesis in ischemic heart failure J. Thorac. Cardiovasc. Surg., April 1, 2009; 137(4): 963 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gnecchi, Z. Zhang, A. Ni, and V. J. Dzau Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy Circ. Res., November 21, 2008; 103(11): 1204 - 1219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Grundmann, N. van Royen, G. Pasterkamp, N. Gonzalez, E. J. Tijsma, J. J. Piek, and I. E. Hoefer A New Intra-Arterial DeliveryPlatform for Pro-Arteriogenic Compounds to Stimulate Collateral Artery Growth Via Transforming Growth Factor-{beta}1 Release J. Am. Coll. Cardiol., July 24, 2007; 50(4): 351 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. W. Zhuang, L. Gao, M. Murakami, J. D. Pearlman, T. J. Sackett, M. Simons, and E. D. de Muinck Arteriogenesis: Noninvasive Quantification with Multi-Detector Row CT Angiography and Three-dimensional Volume Rendering in Rodents Radiology, September 1, 2006; 240(3): 698 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, L. Sun, Y. Huan, H. Zhao, and J. Deng Effects of basic fibroblast growth factor microspheres on angiogenesis in ischemic myocardium and cardiac function: analysis with dobutamine cardiovascular magnetic resonance tagging. Eur. J. Cardiothorac. Surg., July 1, 2006; 30(1): 103 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jin, T. H. Kim, S.-K. Hwang, S.-H. Chang, H. W. Kim, H. K. Anderson, H.-W. Lee, K.-H. Lee, N. H. Colburn, H.-S. Yang, et al. Aerosol delivery of urocanic acid-modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice. Mol. Cancer Ther., April 1, 2006; 5(4): 1041 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Post, K. Sato, M. Murakami, J. Bao, D. Tirziu, J. D. Pearlman, and M. Simons Adenoviral PR39 improves blood flow and myocardial function in a pig model of chronic myocardial ischemia by enhancing collateral formation Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R494 - R500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Cao, A. Hong, H. Schulten, and M. J. Post Update on therapeutic neovascularization Cardiovasc Res, February 15, 2005; 65(3): 639 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Annex and M. Simons Growth factor-induced therapeutic angiogenesis in the heart: protein therapy Cardiovasc Res, February 15, 2005; 65(3): 649 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Schwarz, D. A. Meven, N. Z. Sulemanjee, P. H. Kersting, T. Tussing, E. C. Skobel, P. Hanrath, and B. F. Uretsky Monocyte Chemoattractant Protein 1-Induced Monocyte Infiltration Produces Angiogenesis but Not Arteriogenesis in Chronically Infarcted Myocardium Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 2004; 9(4): 279 - 289. [Abstract] [PDF]
|
|
|
|
 |
|
 G. C. Hughes, S. S. Biswas, B. Yin, R. E. Coleman, T. R. DeGrado, C. K Landolfo, J. E. Lowe, B. H. Annex, and K. P. Landolfo Therapeutic angiogenesis in chronically ischemic porcine myocardium: comparative effects of bFGF and VEGF Ann. Thorac. Surg., March 1, 2004; 77(3): 812 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A.U. Heilmann, T. Attmann, A. Thiem, E. Haffner, F. Beyersdorf, and G. Lutter Gene therapy in cardiac surgery: intramyocardial injection of naked plasmid DNA for chronic myocardial ischemia Eur. J. Cardiothorac. Surg., November 1, 2003; 24(5): 785 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Giordano Retrograde coronary perfusion: a superior route to deliver therapeutics to the heart? J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1129 - 1131. [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Hughes, M. J. Post, M. Simons, and B. H. Annex Translational Physiology: Porcine models of human coronary artery disease: implications for preclinical trials of therapeutic angiogenesis J Appl Physiol, May 1, 2003; 94(5): 1689 - 1701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A.U. Heilmann, T. Attmann, P. von Samson, H. Gobel, D. Marme, F. Beyersdorf, and G. Lutter Transmyocardial laser revascularization combined with vascular endothelial growth factor121 (VEGF121) gene therapy for chronic myocardial ischemia - do the effects really add up? Eur. J. Cardiothorac. Surg., January 1, 2003; 23(1): 74 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Heilmann, P. von Samson, K. Schlegel, T. Attmann, B.-U. von Specht, F. Beyersdorf, and G. Lutter Comparison of protein with DNA therapy for chronic myocardial ischemia using fibroblast growth factor-2 Eur. J. Cardiothorac. Surg., December 1, 2002; 22(6): 957 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ruel, R. J. Laham, J. A. Parker, M. J. Post, J. A. Ware, M. Simons, and F. W. Sellke Long-term effects of surgical angiogenic therapy with fibroblast growth factor 2 protein J. Thorac. Cardiovasc. Surg., July 1, 2002; 124(1): 28 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Khurana, J. F. Martin, and I. Zachary Gene Therapy for Cardiovascular Disease: A Case for Cautious Optimism Hypertension, November 1, 2001; 38(5): 1210 - 1216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Simons, B. H. Annex, R. J. Laham, N. Kleiman, T. Henry, H. Dauerman, J. E. Udelson, E. V. Gervino, M. Pike, M.J. Whitehouse, et al. Pharmacological Treatment of Coronary Artery Disease With Recombinant Fibroblast Growth Factor-2: Double-Blind, Randomized, Controlled Clinical Trial Circulation, February 19, 2002; 105(7): 788 - 793. [Abstract] [Full Text] [PDF]
|
|