Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation

M. E. Vega-Ostertag, D. E. Ferrara, Z. Romay-Penabad, X. Liu, W. R. Taylor, M. Colden-Stanfield, Silvia S. Pierangeli

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Background: The purpose of this study was to examine whether SB 203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor, is effective in reversing the pathogenic effects of antiphospholipid antibodies. Methods: The adhesion of THP-1 monocytes to cultured endothelial cells (EC) treated with immunoglobulin G (IgG) from a patient with antiphospholipid syndrome (IgG-APS) or control IgG (IgG-NHS) in the presence and absence of SB 203580 was examined. The size of an induced thrombus in the femoral vein, the adhesion of leukocytes to EC of cremaster muscle, tissue factor (TF) activity in carotid artery and in peritoneal macrophages, the ex vivo expression of vascular cell adhesion molecule-1 (VCAM-1) in aorta preparations and platelet aggregation were studied in mice injected with IgG-APS or control IgG-NHS and with or without SB 203580. Results: SB 203580 significantly reduced the increased adhesion of THP-1 to EC in vitro, the number of leukocytes adhering to EC, the thrombus size, the TF activity in carotid arteries and in peritoneal mononuclear cells, and the expression of VCAM-1 in aorta of mice, and completely abrogated platelet aggregation induced by IgG-APS. Conclusion: These data suggest that targeting the p38 MAPK pathway may be valuable in designing new therapy modalities for treating thrombosis in patients with APS.

Original languageEnglish (US)
Pages (from-to)1828-1834
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Volume5
Issue number9
DOIs
StatePublished - Sep 2007

Keywords

  • Antiphospholipid antibodies
  • Monocyte adherence
  • p38 MAPK
  • Thrombosis
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Hematology

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    Vega-Ostertag, M. E., Ferrara, D. E., Romay-Penabad, Z., Liu, X., Taylor, W. R., Colden-Stanfield, M., & Pierangeli, S. S. (2007). Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation. Journal of Thrombosis and Haemostasis, 5(9), 1828-1834. https://doi.org/10.1111/j.1538-7836.2007.02680.x