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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4730-4741
Multiple Forms of Angiostatin Induce Apoptosis in Endothelial Cells
R. Lucas,
L. Holmgren,
I. Garcia,
B. Jimenez,
S.J. Mandriota,
F. Borlat,
B.K.L. Sim,
Z. Wu,
G.E. Grau,
Y. Shing,
G.A. Soff,
N. Bouck, and
M.S. Pepper
From the Laboratory of Immunopathology and Laboratory of Intensive
Care, Department of Anesthesiology, Pharmacology, and Surgical
Intensive Care, and Department of Internal Medicine, Geneva University
Hospital, Geneva, Switzerland; the Center for Genomics Research,
Karolinska Institute, Stockholm, Sweden; the Departments of Pathology
and of Morphology, University Medical Center, Geneva, Switzerland; the
Department of Microbiology-Immunology, Division of Hematology-Oncology,
and R.H. Lurie Cancer Center, Northwestern University Medical School,
Chicago, IL; the Serono Pharmaceutical Research Institute S.A., Geneva,
Switzerland; EntreMed Inc, Rockville, MD; and the Department of
Surgical Research, Children's Hospital, Harvard Medical School,
Boston, MA.
Angiostatin is a circulating inhibitor of angiogenesis generated by
proteolytic cleavage of plasminogen. In this study we have used
recombinant human and murine angiostatins (kringles 1-4) as well as
native human angiostatin (prepared by elastase digestion of plasminogen
[kringles 1-3] or by plasmin autocatalysis in the presence of a free
sulfhydryl donor [kringles 1-4]). We report that angiostatin reduces
endothelial cell number in a 4-day proliferation assay without
affecting cell cycle progression into S-phase (as determined by
bromodeoxyuridine labeling). This suggested that the reduction in cell
number in the proliferation assay might in part be due to cytotoxicity.
This was confirmed by the observation that ethidium homodimer
incorporation (a measure of plasma membrane integrity) into endothelial
cells was increased by angiostatin in a manner similar to that seen
with tumor necrosis factor- (TNF-) and transforming growth
factor- 1 (TGF-1), both of which induce apoptosis in endothelial
cells. In contrast to TNF- and TGF-1, angiostatin did not induce
cytotoxicity in human MRC-5 fibroblast, rat smooth muscle, canine MDCK
epithelial, or murine B16-F10 melanoma cell lines. Angiostatin-induced
apoptosis was confirmed by endothelial cell nuclear acridine orange
incorporation as well as by annexin V and TUNEL staining. These in
vitro findings point to endothelial cell apoptosis as a mechanism for
the antiangiogenic effect of angiostatin in vivo.
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|
|
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V. Leksa, S. Godar, H. B. Schiller, E. Fuertbauer, A. Muhammad, K. Slezakova, V. Horejsi, P. Steinlein, U. H. Weidle, B. R. Binder, et al.
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118(19):
4577 - 4586.
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|
|
|
|
|
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|
|
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|
|
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|
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|
|
|
|
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|
|
|
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|
|
|
|
|
|
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278(13):
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[Abstract]
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[PDF]
|
|
|
|
|
|
|
J. Hamacher, R. Lucas, H. R. Lijnen, S. Buschke, Y. Dunant, A. Wendel, G. E. Grau, P. M. Suter, and B. Ricou
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166(5):
651 - 656.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Pfeffer, D. Bisacchi, M. Morini, R. Benelli, S. Minghelli, A. Vacca, D. M. Noonan, and A. Albini
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August 1, 2002;
143(8):
3114 - 3121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Boivin, S. Gendron, E. Beaulieu, D. Gingras, and R. Beliveau
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August 1, 2002;
1(10):
795 - 802.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J. Conti
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August 1, 2002;
7(90003):
4 - 11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Raisler, K. I. Berns, M. B. Grant, D. Beliaev, and W. W. Hauswirth
Adeno-associated virus type-2 expression of pigmented epithelium-derived factor or Kringles 1-3 of angiostatin reduce retinal neovascularization
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June 25, 2002;
99(13):
8909 - 8914.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Chavakis and S. Dimmeler
Regulation of Endothelial Cell Survival and Apoptosis During Angiogenesis
Arterioscler. Thromb. Vasc. Biol.,
June 1, 2002;
22(6):
887 - 893.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-I Ma, P. Guo, J. Li, S.-Z. Lin, Y.-H. Chiang, X. Xiao, and S.-Y. Cheng
Suppression of Intracranial Human Glioma Growth after Intramuscular Administration of an Adeno-associated Viral Vector Expressing Angiostatin
Cancer Res.,
February 1, 2002;
62(3):
756 - 763.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Drixler, I. H. M. B. Rinkes, E. D. Ritchie, F. W. Treffers, T. J. M. V. van Vroonhoven, M. F. B. G. Gebbink, and E. E. Voest
Angiostatin Inhibits Pathological but Not Physiological Retinal Angiogenesis
Invest. Ophthalmol. Vis. Sci.,
December 1, 2001;
42(13):
3325 - 3330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-L. Guo, S. Wang, and R. W. Colman
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Arterioscler. Thromb. Vasc. Biol.,
September 1, 2001;
21(9):
1427 - 1433.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gyorffy, K. Palmer, and J. Gauldie
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Am. J. Pathol.,
September 1, 2001;
159(3):
1137 - 1147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Indraccolo, M. Morini, E. Gola, F. Carrozzino, W. Habeler, S. Minghelli, L. Santi, L. Chieco-Bianchi, Y. Cao, A. Albini, et al.
Effects of Angiostatin Gene Transfer on Functional Properties and in Vivo Growth of Kaposi's Sarcoma Cells
Cancer Res.,
July 1, 2001;
61(14):
5441 - 5446.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gyorffy, K. Palmer, T. J. Podor, M. Hitt, and J. Gauldie
Combined Treatment of a Murine Breast Cancer Model with Type 5 Adenovirus Vectors Expressing Murine Angiostatin and IL-12: A Role for Combined Anti-Angiogenesis and Immunotherapy
J. Immunol.,
May 15, 2001;
166(10):
6212 - 6217.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Troyanovsky, T. Levchenko, G. Mansson, O. Matvijenko, and L. Holmgren
Angiomotin: An Angiostatin Binding Protein That Regulates Endothelial Cell Migration and Tube Formation
J. Cell Biol.,
March 19, 2001;
152(6):
1247 - 1254.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Stellmach, S. E. Crawford, W. Zhou, and N. Bouck
Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor
PNAS,
January 23, 2001;
(2001)
31252398.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. Davis, K. Pintar Allen, R Salazar, and S. Maxwell
Matrix metalloproteinase-1 and -9 activation by plasmin regulates a novel endothelial cell-mediated mechanism of collagen gel contraction and capillary tube regression in three-dimensional collagen matrices
J. Cell Sci.,
January 3, 2001;
114(5):
917 - 930.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. Kuba, K. Matsumoto, K. Date, H. Shimura, M. Tanaka, and T. Nakamura
HGF/NK4, a Four-Kringle Antagonist of Hepatocyte Growth Factor, Is an Angiogenesis Inhibitor that Suppresses Tumor Growth and Metastasis in Mice
Cancer Res.,
December 1, 2000;
60(23):
6737 - 6743.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. Z. Renno, F. C. Delori, R. A. Holzer, E. S. Gragoudas, and J. W. Miller
Photodynamic Therapy Using Lu-Tex Induces Apoptosis In Vitro, and Its Effect Is Potentiated by Angiostatin in Retinal Capillary Endothelial Cells
Invest. Ophthalmol. Vis. Sci.,
November 1, 2000;
41(12):
3963 - 3971.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Amann and E. Ritz
Microvascular disease--the Cinderella of uraemic heart disease
Nephrol. Dial. Transplant.,
October 1, 2000;
15(10):
1493 - 1503.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Dimmeler and A. M. Zeiher
Endothelial Cell Apoptosis in Angiogenesis and Vessel Regression
Circ. Res.,
September 15, 2000;
87(6):
434 - 439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Stefanec
Endothelial Apoptosis: Could It Have a Role in the Pathogenesis and Treatment of Disease?
Chest,
March 1, 2000;
117(3):
841 - 854.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Dignat-George, A. Blann, and J. Sampol
Circulating endothelial cells in acute coronary syndromes
Blood,
January 15, 2000;
95(2):
728 - 728.
[Full Text]
[PDF]
|
|
|
|
