Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4492K) PDF+supp data (6799K) PPT slides of all figures Supplemental Material Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Momi, S. Articles by Gresele, P. PubMed PubMed Citation Articles by Momi, S. Articles by Gresele, P. Social Bookmarking                            What's this?

¹ Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, and ² Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia 06100, Italy
³ Department of Molecular Biomedical Research, Vlaamse Institute of Biotechnology, Ghent 9052, Belgium
⁴ Department of Molecular Biology, Ghent University, Ghent 9000, Belgium

CORRESPONDENCE Paolo Gresele: grespa{at}unipg.it

Platelet activation at a site of vascular injury is essential for the arrest of bleeding; however, excessive platelet activation at a site of arterial damage can result in the unwarranted formation of arterial thrombi, precipitating acute myocardial infarction, or ischemic stroke. Activation of platelets beyond the purpose of hemostasis may occur when substances facilitating thrombus growth and stability accumulate. Human platelets contain matrix metalloproteinase 2 (MMP-2) and release it upon activation. Active MMP-2 amplifies the platelet aggregation response to several agonists by potentiating phosphatidylinositol 3-kinase activation. Using several in vivo thrombosis models, we show that the inactivation of the MMP-2 gene prevented thrombosis induced by weak, but not strong, stimuli in mice but produced only a moderate prolongation of the bleeding time. Moreover, using cross-transfusion experiments and wild-type/MMP-2^–/– chimeric mice, we show that it is platelet-derived MMP-2 that facilitates thrombus formation. Finally, we show that platelets activated by a mild vascular damage induce thrombus formation at a downstream arterial injury site by releasing MMP-2. Thus, platelet-derived MMP-2 plays a crucial role in thrombus formation by amplifying the response of platelets to weak activating stimuli. These findings open new possibilities for the prevention of thrombosis by the development of MMP-2 inhibitors.

Abbreviations used: MMP2, matrix metalloproteinase 2; mRNA, messenger RNA; PI3K, phosphatidylinositol 3-kinase; PRP, platelet-rich plasma.

© 2009 Momi et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Momi, S., Falcinelli, E., Giannini, S., Ruggeri, L., Cecchetti, L., Corazzi, T., Libert, C., Gresele, P. (2009). Loss of matrix metalloproteinase 2 in platelets reduces arterial thrombosis in vivo. JCB 187: i2-i2 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS