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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4714-4720. Prepublished online as a Blood First Edition Paper on January 17, 2006; DOI 10.1182/blood-2005-09-3584. This Article Full Text (PDF) All Versions of this Article: 2005-09-3584v1 107/12/4714    most recent Alert me when this article is cited Alert me if a correction is posted 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 Sun, D. Articles by McCrae, K. R Search for Related Content PubMed PubMed Citation Articles by Sun, D. Articles by McCrae, K. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 6, 2005 Accepted December 17, 2005 Endothelial cell apoptosis induced by cleaved high molecular weight kininogen (HKa) is matrix dependent and requires the generation of reactive oxygen species Danyu Sun and Keith R McCrae* Hematology-Oncology, Case Western Reserve University School of Medicine, Cleveland, OH, USA * Corresponding author; email: keith.mccrae{at}case.edu. High molecular weight kininogen (HK) is an abundant plasma protein that plays a central role in activation of the kallikrein-kinin system. Cleavage of HK by plasma kallikrein results in release of the nonapeptide bradykinin (BK), leaving behind cleaved high molecular weight kininogen (HKa). Previous studies have demonstrated that HKa induces apoptosis of proliferating endothelial cells and inhibits angiogenesis in vivo, activities mediated primarily through its domain 5. However, the mechanisms by which these effects occur are not well understood. Here, we demonstrate that HKa induces apoptosis of endothelial cells cultured on gelatin, vitronectin, fibronectin or laminin, but not collagen types I or IV. The ability of HKa to induce endothelial cell apoptosis is dependent on the generation of intracellular reactive oxygen species, and associated with depletion of glutathione and peroxidation of endothelial cell lipids, effects that occur only in cells cultured on matrix proteins permissive for HKa-induced apoptosis. Finally, the ability of HKa to induce endothelial cell apoptosis is blocked by the addition of reduced glutathione or N-acetyl cysteine. These studies demonstrate a unique role for oxidant stress in mediating the activity of an antiangiogenic polypeptide, and highlight the importance of the extracellular matrix in regulating endothelial cell survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Clapp, S. Thebault, M. C. Jeziorski, and G. Martinez De La Escalera Peptide Hormone Regulation of Angiogenesis Physiol Rev, October 1, 2009; 89(4): 1177 - 1215. [Abstract] [Full Text] [PDF]

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