Semin Thromb Hemost 2000; Volume 26(Number 01): 061-066
DOI: 10.1055/s-2000-9805
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4663)

Angiogenesis and Its Regulation: Roles of Vascular Endothelial Cell Growth Factor

Kazunori Nakagawa, Yong-Xiang Chen, Hiroaki Ishibashi, Yoshikazu Yonemitsu, Toshinori Murata, Yasuaki Hata, Yutaka Nakashima, Katsuo Sueishi
  • Department of Pathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
31. Dezember 2000 (online)

 

ABSTRACT

Neovascularization is well known to occur in human atherosclerotic plaques, proliferative retinopathies, and malignant neoplasias. However, its pathophysiologic roles and mechanisms still remain unclear. In this study, histochemical examination of atherosclerotic plaques showed that vascular endothelial cell growth factor (VEGF) was expressed by the smooth muscle cells and foamy macrophages in the atherosclerotic intimas. The number of VEGF-positive cells was positively correlated with the number of intimal blood vessels. Moreover, VEGF gene transfer into rabbit carotid arteries using the heamagglutinating virus of Japan (HVJ)-liposomes showed that VEGF overexpression could induce the angiomatoid proliferation. In diabetic rats, VEGF was overexpressed in diabetic retinas, and thus the local overexpression of VEGF seemed to play an important role in the development of blood-retinal barrier breakdown in simple diabetic retinopathy. These results indicated that the VEGF can act as a local and endogenous regulator of endothelial cell functions and that VEGF induces the neovascularization under pathopysiologic conditions. On the other hand, the transfer of a decoy for the cis-element in the promoter region of the angiogenic factors would be an effective method for regulating angiogenesis, because other angiogenic factors' expression promoted by such cis-element could be simultaneously suppressed. Therefore, this method may supply a useful therapeutic tool for the regulation of pathologic angiogenesis.

KEYWORD

VEGF - angiogenesis - atherosclerosis - retinopathy - HVJ-liposome

REFERENCES

  • 1 Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor.  Endocrinol Rev . 1997;  18 4-25
    CrossrefPubMedSuche in Google Scholar
  • 2 Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis.  Nature . 1992;  359 843-845
    CrossrefPubMedSuche in Google Scholar
  • 3 Hata Y, Nakagawa K, Ishibashi T. Hypoxia-induced expression of vascular endothelial growth factor by retinal glial cells promotes in vitro angiogenesis.  Virchows Arch . 1995;  426 479-486
    PubMedSuche in Google Scholar
  • 4 Leung D W, Cachianes G, Kuang W J, Goeddel D V, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen.  Science . 1989;  246 1306-1309
    CrossrefPubMedSuche in Google Scholar
  • 5 Keck P J, Hauser S D, Krivi G. Vascular permeability factor, an endothelial cell mitogen related to PDGF.  Science . 1989;  246 1309-1312
    PubMedSuche in Google Scholar
  • 6 Stephan C C, Brock T A. Vascular endothelial growth factor, a multifunctional polypeptide.  PR Health Sci J . 1996;  15 169-178
    PubMedSuche in Google Scholar
  • 7 Dvorak H F, Brown L F, Detmar M, Dvorak A M. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.  Am J Pathol . 1995;  146 1029-1039
    PubMedSuche in Google Scholar
  • 8 Senger D R, Claffey K P, Benes J E. Angiogenesis promoted by vascular endothelial growth factor: Regulation through alpha 1 beta 1 and alpha 2 beta 1 integrins.  Proc Natl Acad Sci USA . 1997;  94 13612-13617
    CrossrefPubMedSuche in Google Scholar
  • 9 Iwasaka C, Tanaka K, Abe M, Sato Y. Ets-1 regulates angiogenesis by inducing the expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells.  J Cell Physiol . 1996;  169 522-531
    CrossrefPubMedSuche in Google Scholar
  • 10 Liu Y, Cox S R, Morita T, Kourembanas S. Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5′enhancer.  Circ Res . 1995;  77 638-643
    CrossrefPubMedSuche in Google Scholar
  • 11 Silins G, Grimmond S, Egerton M, Hayward N. Analysis of the promoter region of the human VEGF-related factor gene.  Biochem Biophys Res Commun . 1997;  230 413-418
    CrossrefPubMedSuche in Google Scholar
  • 12 Damert A, Ikeda E, Risau W. Activator-protein-1 binding potentiates the hypoxia-inducible factor-1-mediated hypoxia-induced transcriptional activation of vascular-endothelial growth factor expression in C6 glioma cells.  Biochem J . 1997;  327 419-423
    PubMedSuche in Google Scholar
  • 13 Minchenko A, Salceda S, Bauer T, Caro J. Hypoxia regulatory elements of the human vascular endothelial growth factor gene.  Cell Mol Biol Res . 1994;  40 35-39
    PubMedSuche in Google Scholar
  • 14 Pepper M S. Manipulating angiogenesis. From basic science to the bedside.  Arterioscler Thromb Biol . 1997;  17 605-619
    PubMedSuche in Google Scholar
  • 15 Morishita R, Sugimoto T, Aoki M. In vivo transfection of cis element ``decoy'' against nuclear factor-kappa B binding site prevents myocardial infarction.  Nat Med . 1997;  3 894-899
    CrossrefPubMedSuche in Google Scholar
  • 16 Chen Y, Nakashima Y, Tanaka K. Immunohistochemical expression of vascular endothelial growth factor/vascular permeability factor (VPF) in the atherosclerotic intimas of human coronary arteries.  Arterioscler Thromb Biol . 1999;  19 131-139
    PubMedSuche in Google Scholar
  • 17 Kumamoto M, Nakashima Y, Sueishi K. Intimal neovascularization in human coronary atherosclerosis: Its origin and pathophysiological significance.  Hum Pathol . 1995;  26 450-456
    CrossrefPubMedSuche in Google Scholar
  • 18 Stary H C, Blankenhorn D H, Chandler A B. A definition of the intima of human arteries and of its atherosclerosis-prone regions. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.  Circulation . 1992;  85 391-405
    CrossrefPubMedSuche in Google Scholar
  • 19 Shiraishi S, Nakagawa K, Kinukawa N, Nakano H, Sueishi K. Immunohistochemical localization of vascular endothelial growth factor in the human placenta.  Placenta . 1996;  17 111-121
    PubMedSuche in Google Scholar
  • 20 Couffinhal T, Kearney M, Witzenbichler B. Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in normal and atherosclerotic human arteries.  Am J Pathol . 1997;  150 1673-1685
    PubMedSuche in Google Scholar
  • 21 Kuzuya M, Satake S, Esaki T. Induction of angiogenesis by smooth muscle cell-derived factor: Possible role in neovascularization in atherosclerotic plaque.  J Cell Physiol . 1995;  164 658-667
    CrossrefPubMedSuche in Google Scholar
  • 22 Yonemitsu Y, Kaneda Y, Morishita R. Characterization of in vivo gene transfer into the arterial wall mediated by the Sendai virus (hemagglutinating virus of Japan) liposomes: An effective tool for the in vivo study of arterial diseases.  Lab Invest . 1996;  75 313-323
    PubMedSuche in Google Scholar
  • 23 Murata T, Nakagawa K, Khalil A. The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas.  Lab Invest . 1996;  74 819-825
    PubMedSuche in Google Scholar
  • 24 Mathews M K, Merges C, McLeod D S, Lutty G A. Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy.  Invest Ophthalmol Vis Sci . 1997;  38 2729-2741
    PubMedSuche in Google Scholar
  • 25 Ryuto M, Ono M, Izumi H. Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells. Possible roles of SP-1.  J Biol Chem . 1996;  271 28220-28228
    CrossrefPubMedSuche in Google Scholar