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

65 Citations (Scopus)

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

Fingerprint

Antiphospholipid Antibodies
p38 Mitogen-Activated Protein Kinases
Thrombosis
Endothelial Cells
Immunoglobulin G
Vascular Cell Adhesion Molecule-1
Thromboplastin
Platelet Aggregation
Carotid Arteries
Aorta
Abdominal Muscles
Antiphospholipid Syndrome
Femoral Vein
Peritoneal Macrophages
Protein Kinase Inhibitors
Leukocyte Count
Cell Size
Monocytes
Cultured Cells
Leukocytes

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

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

Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation. / Vega-Ostertag, M. E.; Ferrara, D. E.; Romay-Penabad, Z.; Liu, X.; Taylor, W. R.; Colden-Stanfield, M.; Pierangeli, Silvia S.

In: Journal of Thrombosis and Haemostasis, Vol. 5, No. 9, 09.2007, p. 1828-1834.

Research output: Contribution to journalArticle

Vega-Ostertag, ME, Ferrara, DE, Romay-Penabad, Z, Liu, X, Taylor, WR, Colden-Stanfield, M & Pierangeli, SS 2007, 'Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation', Journal of Thrombosis and Haemostasis, vol. 5, no. 9, pp. 1828-1834. https://doi.org/10.1111/j.1538-7836.2007.02680.x
Vega-Ostertag, M. E. ; Ferrara, D. E. ; Romay-Penabad, Z. ; Liu, X. ; Taylor, W. R. ; Colden-Stanfield, M. ; Pierangeli, Silvia S. / Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation. In: Journal of Thrombosis and Haemostasis. 2007 ; Vol. 5, No. 9. pp. 1828-1834.
@article{4828801ef7694b95909899b208aac428,
title = "Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation",
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.",
keywords = "Antiphospholipid antibodies, Monocyte adherence, p38 MAPK, Thrombosis, Vascular cell adhesion molecule-1",
author = "Vega-Ostertag, {M. E.} and Ferrara, {D. E.} and Z. Romay-Penabad and X. Liu and Taylor, {W. R.} and M. Colden-Stanfield and Pierangeli, {Silvia S.}",
year = "2007",
month = "9",
doi = "10.1111/j.1538-7836.2007.02680.x",
language = "English (US)",
volume = "5",
pages = "1828--1834",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation

AU - Vega-Ostertag, M. E.

AU - Ferrara, D. E.

AU - Romay-Penabad, Z.

AU - Liu, X.

AU - Taylor, W. R.

AU - Colden-Stanfield, M.

AU - Pierangeli, Silvia S.

PY - 2007/9

Y1 - 2007/9

N2 - 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.

AB - 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.

KW - Antiphospholipid antibodies

KW - Monocyte adherence

KW - p38 MAPK

KW - Thrombosis

KW - Vascular cell adhesion molecule-1

UR - http://www.scopus.com/inward/record.url?scp=34548079756&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548079756&partnerID=8YFLogxK

U2 - 10.1111/j.1538-7836.2007.02680.x

DO - 10.1111/j.1538-7836.2007.02680.x

M3 - Article

C2 - 17723121

AN - SCOPUS:34548079756

VL - 5

SP - 1828

EP - 1834

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 9

ER -