Anti-β₂GPI/β₂GPI complexes induce platelet activation and promote thrombosis via p38MAPK: a pathway to targeted therapies

Abstract

Anti-β₂ glycoprotein I (anti-β₂GPI) antibodies are important contributors to the development of thrombosis. Anti-β₂GPI antibody complexes with β₂GPI are well known to activate monocytes and endothelial cells via the intracellular NF-kB pathway with prothrombotic implications. By contrast, the interaction of anti-β₂GPI/β₂GPI complexes with platelets has not been extensively studied. The p38 mitogen-activated protein kinase (MAPK) pathway has been recognized to be an important intracellular signaling pathway in the coagulation cascade and an integral component of arterial and venous thrombosis. The present study reveals that levels of anti-β₂GPI/β₂GPI complexes in sera are positively associated with p38MAPK phosphorylation of platelets in thrombotic patients. Furthermore, SB203580 inhibits anti-β₂GPI/β₂GPI complex-induced platelet activation. Thrombus formation decreased in p38MAPK^−/− mice after treatment with anti-β₂GPI/β₂GPI complexes. In conclusion, p38MAPK may be a treatment target for anti-β₂GPI antibody-associated thrombotic events.

Keywords

anti-β₂GPI antibody / β₂GPI / platelet / p38MAPK / thrombosis / complex

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Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (No. 81270394) awarded to Yanhong Liu and a grant from the Fundamental Research Founds for the Provincial Universities (No. 2017LCZX67) awarded to Wenjing Zhang.

Compliance with ethics guidelines

Wenjing Zhang, Caijun Zha, Xiumin Lu, Ruichun Ja, Fei Gao, Qi Sun, Meili Jin, and Yanhong Liu declare that they have no financial or other relationships that may lead to a conflict of interest for the present article. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Harbin Medical University Institutional Review Committee, China) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients included in the study. Approval for the animal experimental studies was received from the Institutional Animal Care and Use Committees of Harbin Medical University.

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