© 1996 American Heart Association, Inc.
Articles |
Expression of VEGF Receptors in Arteries After Endothelial Injury and Lack of Increased Endothelial Regrowth in Response to VEGF
the Department of Surgery, Maine Medical Center Research Institute, South Portland, Me (V.H.), and the Department of Pathology, Vascular Biology, University of Washington, Seattle (M.A.R.).
Correspondence to Volkhard Lindner, MD, PhD, Maine Medical Center Research Institute, 125 John Roberts Rd, Suite 8, South Portland, ME 04106. E-mail lindnv.mmcri@office.mmc.org.
Vascular endothelial growth factor (VEGF) is an endothelial cell–specific factor with angiogenic effects in vivo and mitogenic effects in vitro. Administration of VEGF has been reported to stimulate endothelial growth in denuded arteries and new blood vessel formation in models of induced tissue ischemia. In the present study, expression of VEGF and its receptors flk-1 and flt-1 was determined in injured aortas and carotid arteries of rats and mice. Neither VEGF nor flk-1 mRNA was detectable in vascular cells. mRNA levels for flt-1 were dramatically upregulated at the leading edge of a growing endothelial monolayer in vivo; however, these cells did not demonstrate increased replication after VEGF infusion. Furthermore, all doses and treatment protocols of VEGF failed to promote reendothelialization in denuded arteries. At sites of flt-1 expression, VEGF increased permeability. These areas revealed a loss of endothelial contacts at the ultrastructural level. These findings suggest that VEGF is not a direct mitogen for large-vessel endothelium in vivo and that VEGF may play a role in abolishing contact inhibition, which may be a prerequisite for endothelial proliferation.
Key Words: flt-1 • flk-1 • vascular endothelial growth factor • permeability • junctions
This article has been cited by other articles:
 |
|
 |
|
  A. G. Touchard and R. S. Schwartz Preclinical Restenosis Models: Challenges and Successes Toxicol Pathol, January 1, 2006; 34(1): 11 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hutter, F. E. Carrick, C. Valdiviezo, C. Wolinsky, J. S. Rudge, S. J. Wiegand, V. Fuster, J. J. Badimon, and B. V. Sauter Vascular Endothelial Growth Factor Regulates Reendothelialization and Neointima Formation in a Mouse Model of Arterial Injury Circulation, October 19, 2004; 110(16): 2430 - 2435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Schwartz, N. A. Chronos, and R. Virmani Preclinical restenosis models and drug-eluting stents: Still important, still much to learn J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1373 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kishore, C. Luedemann, E. Bord, D. Goukassian, and D. W. Losordo Tumor Necrosis Factor-Mediated E2F1 Suppression in Endothelial Cells: Differential Requirement of c-Jun N-Terminal Kinase and p38 Mitogen-Activated Protein Kinase Signal Transduction Pathways Circ. Res., November 14, 2003; 93(10): 932 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gennaro, C. Menard, S.-E. Michaud, and A. Rivard Age-Dependent Impairment of Reendothelialization After Arterial Injury: Role of Vascular Endothelial Growth Factor Circulation, January 21, 2003; 107(2): 230 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lindner and T. Maciag The Putative Convergent and Divergent Natures of Angiogenesis and Arteriogenesis Circ. Res., October 26, 2001; 89(9): 747 - 749. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Vidal, J. Aragones, A. Alfranca, and M. O. de Landazuri Up-regulation of vascular endothelial growth factor receptor Flt-1 after endothelial denudation: role of transcription factor Egr-1 Blood, June 1, 2000; 95(11): 3387 - 3395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Patterson and M. S. Runge Therapeutic Angiogenesis : The New Electrophysiology? Circulation, May 25, 1999; 99(20): 2614 - 2616. [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-X. Chen, Y. Nakashima, K. Tanaka, S. Shiraishi, K. Nakagawa, and K. Sueishi Immunohistochemical Expression of Vascular Endothelial Growth Factor/Vascular Permeability Factor in Atherosclerotic Intimas of Human Coronary Arteries Arterioscler. Thromb. Vasc. Biol., January 1, 1999; 19(1): 131 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. M. van Beusekom, D. M. Whelan, S. H. Hofma, S. C. Krabbendam, V. W. M. van Hinsbergh, P. D. Verdouw, and W. J. van der Giessen Long-term endothelial dysfunction is more pronounced after stenting than after balloon angioplasty in porcine coronary arteries J. Am. Coll. Cardiol., October 1, 1998; 32(4): 1109 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
L. L. Couper, S. R. Bryant, J. Eldrup-Jorgensen, C. E. Bredenberg, and V. Lindner Vascular Endothelial Growth Factor Increases the Mitogenic Response to Fibroblast Growth Factor-2 in Vascular Smooth Muscle Cells In Vivo via Expression of fms-Like Tyrosine Kinase-1 Circ. Res., December 19, 1997; 81(6): 932 - 939. [Abstract] [Full Text]
|
|
|
|
|
|
E. Deindl, I. Buschmann, I. E. Hoefer, T. Podzuweit, K. Boengler, S. Vogel, N. van Royen, B. Fernandez, and W. Schaper Role of Ischemia and of Hypoxia-Inducible Genes in Arteriogenesis After Femoral Artery Occlusion in the Rabbit Circ. Res., October 26, 2001; 89(9): 779 - 786. [Abstract] [Full Text] [PDF]
|
|