Circulation, Vol 89, 2183-2189, Copyright © 1994 by American Heart Association
S Banai, MT Jaklitsch, M Shou, DF Lazarous, M Scheinowitz, S Biro, SE Epstein and EF Unger
BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial
cell-specific mitogen that is angiogenic in vitro and in vivo. It has been
hypothesized that VEGF plays a role in myocardial collateral formation;
however, the effects of VEGF on collateral flow to ischemic myocardium are
unknown. METHODS AND RESULTS: We studied the effect of VEGF on collateral
blood flow in dogs subjected to gradual occlusion of the left circumflex
coronary artery (LCx). Beginning 10 days after placement of an
LCx-constricting device, VEGF 45 micrograms (n = 9) or saline (n = 12) was
administered daily via an indwelling catheter in the distal LCx, at a point
just beyond the occlusion. Treatment was maintained for 28 days. Collateral
blood flow was determined with microspheres 7 days before treatment,
immediately before treatment (day 0), and 7, 14, 21, and 28 days into the
treatment period. Collateral blood flow was quantified during
chromonar-induced maximal vasodilation and expressed as a collateral
zone/normal zone (CZ/NZ) ratio. Treatment with VEGF was associated with a
40% increase in collateral blood flow (final CZ/NZ blood flow ratios of
0.49 +/- 0.06 and 0.35 +/- 0.02 in the VEGF-treated and control groups,
respectively, P = .0037) as well as an 89% increase in the numerical
density of intramyocardial distribution vessels (> 20 microns diameter)
in the CZ (6.6 +/- 1.4 versus 3.5 +/- 0.7 vessels/mm2 in VEGF-treated and
control dogs, respectively, P < .05). CONCLUSIONS: We conclude that
intracoronary VEGF enhances the development of small coronary arteries
supplying ischemic myocardium, resulting in marked augmentation of maximal
collateral blood flow delivery. These results demonstrate the feasibility
of pharmacological enhancement of collateral growth and suggest a new
therapeutic approach for the treatment of myocardial ischemia.
ARTICLES
Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. 20892.
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D. F Lazarous, M. Shou, J. A Stiber, E. Hodge, V. Thirumurti, L. Goncalves, and E. F Unger Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis Cardiovasc Res, November 1, 1999; 44(2): 294 - 302. [Abstract] [Full Text] [PDF]
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J. F. Symes, D. W. Losordo, P. R. Vale, K. G. Lathi, D. D. Esakof, M. Mayskiy, and J. M. Isner Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease Ann. Thorac. Surg., September 1, 1999; 68(3): 830 - 836. [Abstract] [Full Text] [PDF]
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 T. Asahara, H. Masuda, T. Takahashi, C. Kalka, C. Pastore, M. Silver, M. Kearne, M. Magner, and J. M. Isner Bone Marrow Origin of Endothelial Progenitor Cells Responsible for Postnatal Vasculogenesis in Physiological and Pathological Neovascularization Circ. Res., August 6, 1999; 85(3): 221 - 228. [Abstract] [Full Text] [PDF]
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A. Schultz, L. Lavie, I. Hochberg, R. Beyar, T. Stone, K. Skorecki, P. Lavie, A. Roguin, and A. P. Levy Interindividual Heterogeneity in the Hypoxic Regulation of VEGF : Significance for the Development of the Coronary Artery Collateral Circulation Circulation, August 3, 1999; 100(5): 547 - 552. [Abstract] [Full Text] [PDF]
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O. Reuthebuch, T. Podzuweit, S. Thomas, K. Binz, M. Roth, W.-P. Klovekorn, and E. P. Bauer Transmyocardial laser revascularisation has no beneficial effect on high energy phosphates and lactate content during acute myocardial ischaemia in pigs Eur. J. Cardiothorac. Surg., August 1, 1999; 16(2): 144 - 149. [Abstract] [Full Text] [PDF]
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W. Zheng, M. D. Brown, T. A. Brock, R. J. Bjercke, and R. J. Tomanek Bradycardia-Induced Coronary Angiogenesis Is Dependent on Vascular Endothelial Growth Factor Circ. Res., July 23, 1999; 85(2): 192 - 198. [Abstract] [Full Text] [PDF]
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 R. J. Laham, M. Rezaee, M. Post, F. W. Sellke, R. A. Braeckman, D. Hung, and M. Simons Intracoronary and Intravenous Administration of Basic Fibroblast Growth Factor: Myocardial and Tissue Distribution Drug Metab. Dispos., July 1, 1999; 27(7): 821 - 826. [Abstract] [Full Text]
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P. R. Vale, D. W. Losordo, T. Tkebuchava, D. Chen, C. E. Milliken, and J. M. Isner Catheter-based myocardial gene transfer utilizing nonfluoroscopic electromechanical left ventricular mapping J. Am. Coll. Cardiol., July 1, 1999; 34(1): 246 - 254. [Abstract] [Full Text] [PDF]
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J. R Kersten, P. S Pagel, W. M Chilian, and D. C Warltier Multifactorial basis for coronary collateralization: a complex adaptive response to ischemia Cardiovasc Res, July 1, 1999; 43(1): 44 - 57. [Abstract] [Full Text] [PDF]
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 Y. Fujio and K. Walsh Akt Mediates Cytoprotection of Endothelial Cells by Vascular Endothelial Growth Factor in an Anchorage-dependent Manner J. Biol. Chem., June 4, 1999; 274(23): 16349 - 16354. [Abstract] [Full Text] [PDF]
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R. Morishita, S. Nakamura, S.-i. Hayashi, Y. Taniyama, A. Moriguchi, T. Nagano, M. Taiji, H. Noguchi, S. Takeshita, K. Matsumoto, et al. Therapeutic Angiogenesis Induced by Human Recombinant Hepatocyte Growth Factor in Rabbit Hind Limb Ischemia Model as Cytokine Supplement Therapy Hypertension, June 1, 1999; 33(6): 1379 - 1384. [Abstract] [Full Text] [PDF]
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S. Kanno, N. Oda, M. Abe, S. Saito, K. Hori, Y. Handa, K. Tabayashi, and Y. Sato Establishment of a Simple and Practical Procedure Applicable to Therapeutic Angiogenesis Circulation, May 25, 1999; 99(20): 2682 - 2687. [Abstract] [Full Text] [PDF]
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A. Abaci, S. Kahraman, N. K. Eryol, H. Arinc, and A. Ergin Effect of Diabetes Mellitus on Formation of Coronary Collateral Vessels Circulation, May 4, 1999; 99(17): 2239 - 2242. [Abstract] [Full Text] [PDF]
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 A. Rivard, M. Silver, D. Chen, M. Kearney, M. Magner, B. Annex, K. Peters, and J. M. Isner Rescue of Diabetes-Related Impairment of Angiogenesis by Intramuscular Gene Therapy with Adeno-VEGF Am. J. Pathol., February 1, 1999; 154(2): 355 - 363. [Abstract] [Full Text] [PDF]
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A. Rivard, J.-E. Fabre, M. Silver, D. Chen, T. Murohara, M. Kearney, M. Magner, T. Asahara, and J. M. Isner Age-Dependent Impairment of Angiogenesis Circulation, January 12, 1999; 99(1): 111 - 120. [Abstract] [Full Text] [PDF]
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 M. J. Acarregui, S. T. Penisten, K. L. Goss, K. Ramirez, and J. M. Snyder Vascular Endothelial Growth Factor Gene Expression in Human Fetal Lung In Vitro Am. J. Respir. Cell Mol. Biol., January 1, 1999; 20(1): 14 - 23. [Abstract] [Full Text]
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D. W. Losordo, P. R. Vale, J. F. Symes, C. H. Dunnington, D. D. Esakof, M. Maysky, A. B. Ashare, K. Lathi, and J. M. Isner Gene Therapy for Myocardial Angiogenesis : Initial Clinical Results With Direct Myocardial Injection of phVEGF165 as Sole Therapy for Myocardial Ischemia Circulation, December 22, 1998; 98(25): 2800 - 2804. [Abstract] [Full Text] [PDF]
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R. J. Laham, M. Simons, M. Tofukuji, D. Hung, and F. W. Sellke MODULATION OF MYOCARDIAL PERFUSION AND VASCULAR REACTIVITY BY PERICARDIAL BASIC FIBROBLAST GROWTH FACTOR: INSIGHT INTO ISCHEMIA-INDUCED REDUCTION IN ENDOTHELIUM-DEPENDENT VASODILATATION J. Thorac. Cardiovasc. Surg., December 1, 1998; 116(6): 1022 - 1028. [Abstract] [Full Text] [PDF]
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J. J Lopez, R. J. Laham, A. Stamler, J. D Pearlman, S. Bunting, A. Kaplan, J. P Carrozza, F. W Sellke, and M. Simons VEGF administration in chronic myocardial ischemia in pigs Cardiovasc Res, November 1, 1998; 40(2): 272 - 281. [Abstract] [Full Text] [PDF]
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D. Weihrauch, J. Tessmer, D. C. Warltier, and W. M. Chilian Repetitive coronary artery occlusions induce release of growth factors into the myocardial interstitium Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H969 - H976. [Abstract] [Full Text] [PDF]
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T. Asahara, D. Chen, T. Takahashi, K. Fujikawa, M. Kearney, M. Magner, G. D. Yancopoulos, and J. M. Isner Tie2 Receptor Ligands, Angiopoietin-1 and Angiopoietin-2, Modulate VEGF-Induced Postnatal Neovascularization Circ. Res., August 10, 1998; 83(3): 233 - 240. [Abstract] [Full Text] [PDF]
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B. Witzenbichler, T. Asahara, T. Murohara, M. Silver, I. Spyridopoulos, M. Magner, N. Principe, M. Kearney, J.-S. Hu, and J. M. Isner Vascular Endothelial Growth Factor-C (VEGF-C/VEGF-2) Promotes Angiogenesis in the Setting of Tissue Ischemia Am. J. Pathol., August 1, 1998; 153(2): 381 - 394. [Abstract] [Full Text] [PDF]
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F. Xu and J. W. Severinghaus Rat brain VEGF expression in alveolar hypoxia: possible role in high-altitude cerebral edema J Appl Physiol, July 1, 1998; 85(1): 53 - 57. [Abstract] [Full Text] [PDF]
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R. J. Tomanek, K. Lotun, E. B. Clark, P. R. Suvarna, and N. Hu VEGF and bFGF stimulate myocardial vascularization in embryonic chick Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1620 - H1626. [Abstract] [Full Text] [PDF]
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E. Van Belle, C. Bauters, T. Asahara, and J. M. Isner Endothelial regrowth after arterial injury: from vascular repair to therapeutics Cardiovasc Res, April 1, 1998; 38(1): 54 - 68. [Full Text] [PDF]
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I. Baumgartner, A. Pieczek, O. Manor, R. Blair, M. Kearney, K. Walsh, and J. M. Isner Constitutive Expression of phVEGF165 After Intramuscular Gene Transfer Promotes Collateral Vessel Development in Patients With Critical Limb Ischemia Circulation, March 31, 1998; 97(12): 1114 - 1123. [Abstract] [Full Text] [PDF]
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J. J. Lopez, E. R. Edelman, A. Stamler, M. G. Hibberd, P. Prasad, K. A. Thomas, J. Disalvo, R. P. Caputo, J. P. Carrozza, P. S. Douglas, et al. Angiogenic potential of perivascularly delivered aFGF in a porcine model of chronic myocardial ischemia Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H930 - H936. [Abstract] [Full Text] [PDF]
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E. Van Belle, B. Witzenbichler, D. Chen, M. Silver, L. Chang, R. Schwall, and J. M. Isner Potentiated Angiogenic Effect of Scatter Factor/Hepatocyte Growth Factor via Induction of Vascular Endothelial Growth Factor : The Case for Paracrine Amplification of Angiogenesis Circulation, February 3, 1998; 97(4): 381 - 390. [Abstract] [Full Text] [PDF]
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T. Murohara, J. R. Horowitz, M. Silver, Y. Tsurumi, D. Chen, A. Sullivan, and J. M. Isner Vascular Endothelial Growth Factor/Vascular Permeability Factor Enhances Vascular Permeability Via Nitric Oxide and Prostacyclin Circulation, January 13, 1998; 97(1): 99 - 107. [Abstract] [Full Text] [PDF]
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