Abstract
Rationale: Besides their essential role in hemostasis, platelets also have functions in inflammation. In platelets, junctional adhesion molecule (JAM)-A was previously identified as an inhibitor of integrin alpha(IIb)beta(3)-mediated outside-in signaling and its genetic knockdown resulted in hyperreactivity. Objective: This gain-of-function was specifically exploited to investigate the role of platelet hyperreactivity in plaque development. Methods and Results: JAM-A-deficient platelets showed increased aggregation and cellular and sarcoma tyrosine-protein kinase activation. On alpha(IIb)beta(3) ligation, JAM-A was shown to be dephosphorylated, which could be prevented by protein tyrosine phosphatase nonreceptor type 1 inhibition. Mice with or without platelet-specific (tr) JAM-A-deficiency in an apolipoprotein e (apoe(-/-)) background were fed a high-fat diet. After
Original language | English |
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Pages (from-to) | 587-599 |
Journal | Circulation Research |
Volume | 116 |
Issue number | 4 |
DOIs | |
Publication status | Published - 13 Feb 2015 |
Keywords
- atherosclerosis
- blood platelets
- cell adhesion molecules
- inflammation
- phosphoprotein phosphatases