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Blood, 30 April 2009, Vol. 113, No. 18, pp. 4431-4439. Prepublished online as a Blood First Edition Paper on December 12, 2008; DOI 10.1182/blood-2008-07-169433. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-169433v1 113/18/4431    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 Guo, Y.-H. Articles by Weiler, H. Search for Related Content PubMed PubMed Citation Articles by Guo, Y.-H. Articles by Weiler, H. Related Collections Thrombosis and Hemostasis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Caveolin-1–dependent apoptosis induced by fibrin degradation products Yi-He Guo1, Irene Hernandez1, Berend Isermann1, Tae-bong Kang2, Leonid Medved3, Rashmi Sood1, Edward J. Kerschen1, Trudy Holyst1, Michael W. Mosesson1, and Hartmut Weiler1 1 Blood Research Institute, BloodCenter of Wisconsin, Milwaukee; 2 Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel; and 3 Center for Vascular and Inflammatory Diseases and the Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore In mice lacking the blood coagulation regulator thrombomodulin, fibrinolytic degradation products (FDP) of fibrin induce apoptotic cell death of a specialized cell type in the placenta, polyploid trophoblast giant cells. Here, we document that this bioactivity of FDP is conserved in human FDP, is not limited to trophoblast cells, and is associated with an A-chain segment of fibrin fragment E (FnE). The majority of proapoptotic activity is arginine-glycine-aspartic acid (RGD)-independent and requires caveolin-1–dependent cellular internalization of FnE. Internalization through caveoli is mediated by an epitope contained within A52-81 that is necessary and sufficient for cellular uptake of FnE. A52-81 does not cause apoptosis itself, and competitively inhibits FnE internalization and apoptosis induction. Apoptotic activity per se resides within A17-37 and requires the N-terminal neoepitope generated by release of fibrinopeptide A. Cellular internalization of FnE elicits depression of mitochondrial function and consequent apoptosis that is strictly dependent on the activity of caspases 9 and 3. These findings describe the molecular details of a novel mechanism linking fibrin degradation to cell death in the placenta, which may also contribute to pathologic alterations in nonplacental vascular beds that are associated with fibrinolysis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: How can fibrinolysis induce cell death? Margarethe Geiger Blood 2009 113: 4134-4135. [Full Text] [PDF] This article has been cited by other articles: M. Geiger How can fibrinolysis induce cell death? Blood, April 30, 2009; 113(18): 4134 - 4135. [Full Text] [PDF]

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