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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-01-0185. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-01-0185v1 100/9/3245    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Miao, R. Q. Articles by Chao, J. Search for Related Content PubMed PubMed Citation Articles by Miao, R. Q. Articles by Chao, J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 November 2002, Vol. 100, No. 9, pp. 3245-3252 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Kallistatin is a new inhibitor of angiogenesis and tumor growth Robert Q. Miao, Jun Agata, Lee Chao, and Julie Chao From the Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston. Kallistatin is a unique serine proteinase inhibitor (serpin) and a heparin-binding protein. It has been localized in vascular smooth muscle cells and endothelial cells of human blood vessels, suggesting that kallistatin may be involved in the regulation of vascular function. Our previous study showed that kallistatin plays a role in neointima hyperplasia. In this study, we investigated the potential role of kallistatin in angiogenesis in vitro and in vivo. Purified human kallistatin significantly inhibited vascular endothelial growth factor (VEGF)- or basic fibroblast growth factor (bFGF)-induced proliferation, migration, and adhesion of cultured endothelial cells. Kallistatin attenuated VEGF- or bFGF-induced capillary density and hemoglobin content in subcutaneously implanted Matrigel plugs in mice. To further investigate the role of kallistatin in angiogenesis, we prepared adenovirus carrying the human kallistatin cDNA (Ad.HKBP) and evaluated the effect of kallistatin gene delivery on spontaneous angiogenesis in a rat model of hind-limb ischemia. Local kallistatin gene delivery significantly reduced capillary formation and regional blood perfusion recovery in the ischemic hind limb after removal of the femoral artery. Furthermore, a single intratumoral injection of Ad.HKBP into pre-established human breast tumor xenografts grown in athymic mice resulted in significant inhibition of tumor growth. CD31 immunostaining of tumor sections showed a decreased number of blood vessels in the kallistatin-treated group as compared to the control. These results demonstrate a novel role of kallistatin in the inhibition of angiogenesis and tumor growth. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Vincent, P. Bonnin, M. Clemessy, J.-O. Contreres, N. Lamande, J.-M. Gasc, J. Vilar, P. Hainaud, G. Tobelem, P. Corvol, et al. Angiotensinogen Delays Angiogenesis and Tumor Growth of Hepatocarcinoma in Transgenic Mice Cancer Res., April 1, 2009; 69(7): 2853 - 2860. [Abstract] [Full Text] [PDF] B. Richard, R. Swanson, S. Schedin-Weiss, B. Ramirez, G. Izaguirre, P. G. W. Gettins, and S. T. Olson Characterization of the Conformational Alterations, Reduced Anticoagulant Activity, and Enhanced Antiangiogenic Activity of Prelatent Antithrombin J. Biol. 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