© 1994 by European Society of Cardiology
Copyright © 1994, European Society of Cardiology
Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis
Heiden Department of Cardiology, Bikur Cholim Hospital, PO Box 492, Jerusalem 91002, Israel: S Banai; Department of Molecular Biology, The Hebrew University Medical School, Jerusalem: D Shweiki, A Pinson, E Keshet; Laboratory for Experimental Cardiac Surgery, Hadassah Medical Centre, Jerusalem: M Chandra, G Lazarovici.
Correspondence to Dr Banai.
Objective: The process of coronary collateral development is poorly understood. It is assumed that particular angiogenic factors are upregulated during episodes of myocardial ischaemia and act as a trigger for neovascularisation. However, the identity of these factors is unknown. The angiogenic factor vascular endothelial growth factor (VEGF) has been shown to be hypoxia inducible, so this factor may mediate ischaemia induced angiogenesis in the heart. The aim of this study was to examine hypoxia inducibility of VEGF in cultured myocardial cells as well as in normally perfused and ischaemic porcine myocardium. Methods: (1) In vitro experiment: cultured rat myocardial cells were subjected to hypoxia, and steady state levels of VEGF mRNA were measured after 2 and 4 h of hypoxia. (2) In vivo experiment: myocardial ischaemia in pigs hearts was induced by repeated 2-10 min left anterior descending coronary artery occlusions, separated by 20 min of reperfusion. Hearts were retrieved after 6 h of intermittent ischaemia. Total RNA was extracted from normal and ischaemic zones of the heart and processed for RNA blot hybridisation analysis. Results: In vitro experiment: as soon as 2-4 h after exposure of cultures to hypoxia, VEGF mRNA levels were significantly raised (6-10-fold). In vivo experiment: VEGF expression was significantly augmented in the ischaemic territory of the myocardium (three- to fivefold induction). Furthermore, polymerase chain reaction amplification of the reverse transcribed mRNA showed increased production of multiple forms of differentially spliced VEGF mRNA in the ischaemic myocardium. Conclusions: VEGF production in the myocardium is significantly upregulated by hypoxia in vitro and by ischaemia in vivo. These results suggest that VEGF is a likely mediator in the natural process of ischaemia induced myocardial neovascularisation.
Cardiovascular Research 1994;28:1176-1179
KEYWORDS coronary collateral vessels; hypoxia; neovascularisation
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P. Carmeliet and D. Collen Molecular analysis of blood vessel formation and disease Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2091 - H2104. [Abstract] [Full Text] [PDF]
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S.-Y. Cheng, M. Nagane, H.-J. S. Huang, and W. K. Cavenee Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189 PNAS, October 28, 1997; 94(22): 12081 - 12087. [Abstract] [Full Text] [PDF]
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P. Salven, L. Teerenhovi, and H. Joensuu A High Pretreatment Serum Vascular Endothelial Growth Factor Concentration Is Associated With Poor Outcome in Non-Hodgkin's Lymphoma Blood, October 15, 1997; 90(8): 3167 - 3172. [Abstract] [Full Text] [PDF]
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Z. Luo, M. Diaco, T. Murohara, N. Ferrara, J. M. Isner, and J. F. Symes Vascular Endothelial Growth Factor Attenuates Myocardial Ischemia-Reperfusion Injury Ann. Thorac. Surg., October 1, 1997; 64(4): 993 - 998. [Abstract] [Full Text]
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D. S. Winlaw Angiogenesis in the Pathobiology and Treatment of Vascular and Malignant Diseases Ann. Thorac. Surg., October 1, 1997; 64(4): 1204 - 1211. [Abstract] [Full Text]
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B. S Lewis, M. Y Flugelman, A. Weisz, I. Keren-Tal, and W. Schaper Angiogenesis by gene therapy: a new horizon for myocardial revascularization? Cardiovasc Res, September 1, 1997; 35(3): 490 - 497. [Abstract] [Full Text] [PDF]
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H. Abedi and I. Zachary Vascular Endothelial Growth Factor Stimulates Tyrosine Phosphorylation and Recruitment to New Focal Adhesions of Focal Adhesion Kinase and Paxillin in Endothelial Cells J. Biol. Chem., June 13, 1997; 272(24): 15442 - 15451. [Abstract] [Full Text] [PDF]
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 R. O SCHLINGEMANN and V. W M VAN HINSBERGH Role of vascular permeability factor/vascular endothelial growth factor in eye disease Br J Ophthalmol, June 1, 1997; 81(6): 501 - 512. [Full Text] [PDF]
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M. Ema, S. Taya, N. Yokotani, K. Sogawa, Y. Matsuda, and Y. Fujii-Kuriyama A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development PNAS, April 29, 1997; 94(9): 4273 - 4278. [Abstract] [Full Text] [PDF]
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 M. S. Pepper Manipulating Angiogenesis: From Basic Science to the Bedside Arterioscler Thromb Vasc Biol, April 1, 1997; 17(4): 605 - 619. [Abstract] [Full Text]
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W. Schaper and W. D. Ito Molecular Mechanisms of Coronary Collateral Vessel Growth Circ. Res., November 1, 1996; 79(5): 911 - 919. [Full Text]
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 Z. Kovacs, K. Ikezaki, K. Samoto, T. Inamura, M. Fukui, T. Kawamata, and S. P. Finklestein VEGF and flt: Expression Time Kinetics in Rat Brain Infarct Stroke, October 1, 1996; 27(10): 1865 - 1873. [Abstract] [Full Text]
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J. Waltenberger, U. Mayr, S. Pentz, and V. Hombach Functional Upregulation of the Vascular Endothelial Growth Factor Receptor KDR by Hypoxia Circulation, October 1, 1996; 94(7): 1647 - 1654. [Abstract] [Full Text]
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C. J. Magovern, C. A. Mack, J. Zhang, R. T. Hahn, W. Ko, O. W. Isom, R. G. Crystal, and T. K. Rosengart Direct In Vivo Gene Transfer to Canine Myocardium Using a Replication-Deficient Adenovirus Vector Ann. Thorac. Surg., August 1, 1996; 62(2): 425 - 433. [Abstract] [Full Text]
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K. A. Thomas and K. A. Thomas Vascular Endothelial Growth Factor, a Potent and Selective Angiogenic Agent J. Biol. Chem., January 12, 1996; 271(2): 603 - 606. [Full Text] [PDF]
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J. C.-C. Tsang and R. C.-J. Chiu The Phantom of ``Myocardial Sinusoids'': A Historical Reappraisal Ann. Thorac. Surg., December 1, 1995; 60(6): 1831 - 1835. [Abstract] [Full Text]
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G. T. Stavri, I. C. Zachary, P. A. Baskerville, J. F. Martin, and J. D. Erusalimsky Basic Fibroblast Growth Factor Upregulates the Expression of Vascular Endothelial Growth Factor in Vascular Smooth Muscle Cells : Synergistic Interaction With Hypoxia Circulation, July 1, 1995; 92(1): 11 - 14. [Abstract] [Full Text]
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W. Casscells Growth Factor Therapies for Vascular Injury and Ischemia Circulation, June 1, 1995; 91(11): 2699 - 2702. [Full Text]
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A. Rivard, L. Berthou-Soulie, N. Principe, M. Kearney, C. Curry, D. Branellec, G. L. Semenza, and J. M. Isner Age-dependent Defect in Vascular Endothelial Growth Factor Expression Is Associated with Reduced Hypoxia-inducible Factor 1 Activity J. Biol. Chem., September 15, 2000; 275(38): 29643 - 29647. [Abstract] [Full Text] [PDF]
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M. D. Mueller, J.-L. Vigne, A. Minchenko, D. I. Lebovic, D. C. Leitman, and R. N. Taylor Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta PNAS, September 26, 2000; 97(20): 10972 - 10977. [Abstract] [Full Text] [PDF]
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H. Kawata, K.-i. Yoshida, A. Kawamoto, H. Kurioka, E. Takase, Y. Sasaki, K. Hatanaka, M. Kobayashi, T. Ueyama, T. Hashimoto, et al. Ischemic Preconditioning Upregulates Vascular Endothelial Growth Factor mRNA Expression and Neovascularization via Nuclear Translocation of Protein Kinase C {epsilon} in the Rat Ischemic Myocardium Circ. Res., April 13, 2001; 88(7): 696 - 704. [Abstract] [Full Text] [PDF]
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