Pathophysiology of Thrombosis and Potential Targeted Therapies in Antiphospholipid Syndrome

Author(s): Olga Amengual, Tatsuya Atsumi, Takao Koike.

Journal Name: Current Vascular Pharmacology

Volume 9 , Issue 5 , 2011

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Abstract:

The antiphospholipid syndrome (APS) is an autoimmune disease in which recurrent vascular thrombosis, pregnancy morbidity or a combination of these events is associated with the persistent presence of circulating antiphospholipid antibodies (aPL). Evidence shows that the dominant antigenic targets for aPL in APS are phospholipid-binding plasma proteins such as β2glycoprotein I and prothrombin. The pathogenic role of aPL in thrombosis is widely accepted but the mechanisms by which these antibodies mediate disease are only partially understood. aPL may affect the normal procoagulant and anticoagulant reactions occurring on cell surface, and also may interact with certain cells, altering the expression and secretion of procoagulant substances. The intracellular signal transduction triggered by aPL has been a focus of intensive research and the p38 mitogen activated protein kinase (MAPK) pathway has been revealed as a major player in the aPL-mediated cell activation. In addition, some candidates as cell-receptor for phospholipid-binding plasma proteins have been identified. The recognition of the intracellular signaling triggered by aPL is a step forward in the design of new modalities of targeted therapies for thrombosis in APS including specific inhibitors of MAPK pathway or antagonists of the putative receptors. Furthermore, novel findings regarding the role of aPL in T-cells responses mark new advances in the understanding of the immunological reactions in APS and open new insights into possible therapeutic approaches to APS. In this article, we review the pathophysiological mechanisms of thrombosis and the specific new targeted therapies for the treatment in APS.

Keywords: Antiphospholipid antibodies, p38MAPK, β2GPI, prothrombin, tissue factor, antiphospholipid syndrome, thrombosis, psychiatric manifestations, nephropathy, pulmonary hypertension

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Article Details

VOLUME: 9
ISSUE: 5
Year: 2011
Page: [606 - 618]
Pages: 13
DOI: 10.2174/157016111796642715
Price: $58

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