Hyperreactivity of Junctional Adhesion Molecule A-Deficient Platelets Accelerates Atherosclerosis in Hyperlipidemic Mice

Ela Karshovska, Zhen Zhao, Xavier Blanchet, Martin M. N. Schmitt, Kiril Bidzhekov, Oliver Soehnlein, Philipp von Hundelshausen, Nadine J. Mattheij, Judith M. E. M. Cosemans, Remco T. A. Megens, Thomas A. Koeppel, Andreas Schober, Tilman M. Hackeng, Christian Weber, Rory R. Koenen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 languageEnglish
Pages (from-to)587-599
JournalCirculation Research
Issue number4
Publication statusPublished - 13 Feb 2015


  • atherosclerosis
  • blood platelets
  • cell adhesion molecules
  • inflammation
  • phosphoprotein phosphatases

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