Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of tissue factor activity on cells in contact with flowing blood is the trigger for physiological coagulation as well as many types of thrombosis. A number of older observations and considerable recent data suggest that increased tissue factor activity is an important cause of hypercoagulability in the antiphospholipid syndrome. Potential mechanisms contributing to upregulation of the tissue factor pathway include increased expression of tissue factor due to increased transcription, increased functional activity of tissue factor molecules due to de-encryption and decreased activity of tissue factor pathway inhibitor. Autoantibodies and/or immune complexes appear to play a major role in enhanced tissue factor activity, although increased levels of inflammatory cytokines may also contribute. Anti-beta 2-glycoprotein I autoantibodies have been specifically implicated in the antibody-mediated enhancement of tissue factor activity.
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PMID:Tissue factor pathway and the antiphospholipid syndrome. 1096 13

On the basis of the role of immuno-mediated inflammation in atherosclerosis we investigated, (1) the prevalence of anti-endothelial cell antibodies (AECA) in ischaemic heart disease (IHD); (2) if beta2-glycoprotein I (beta2-GPI) was the target antigen of AECA; (3) the relationship between AECA, tissue factor (TF) and tissue factor pathway inhibitor (TFPI). In 93 consecutive IHD patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and 105 controls AECA were detected by ELISA on human umbilical vein endothelial cells (HUVEC). AECA positive sera were evaluated for anti-beta2-GPI antibodies by ELISA. TF and TFPI plasma levels were assessed by ELISA. Twelve of 93 (12.9%) IHD patients and only one of 105 controls (0.95%) were AECA positive. The prevalence of AECA was higher in unstable angina (UA) than in effort angina (EA) (P=0.01). Three of 12 AECA positive sera resulted positive for anti-beta2-GPI and showed a marked decrease in EC-binding when tested on HUVEC cultured in serum-free medium. The binding was restored by the addition of beta2-GPI. TF and TFPI levels were similar in AECA positive and AECA negative patients. The rate of angiographically documented clinical recurrences was 66.7% in the AECA positive and 14.8% in the AECA negative group (P=0.0004) with a significant relationship between restenosis and AECA (P<0.0001), unchanged by the inclusion of cardiovascular risk factors in the regression model. Our results suggest a 'role' for AECA in the immune-mediated inflammation in UA beta2-GPI is not the only AECA target antigen. AECA are not responsible for high TF and TFPI levels. The high rate of clinical recurrences after PTCA, confirmed by angiography, in AECA positive patients is in line with such a role and suggests further large-scale 'ad hoc' studies.
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PMID:Activation of the immune system and coronary artery disease: the role of anti-endothelial cell antibodies. 1116 76

The expression of tissue factor (TF) activity to flowing blood is the trigger for physiological coagulation as well as many types of thrombosis. A growing body of evidence suggests that increased tissue factor activity is a significant contributor towards the hypercoagulability associated with the antiphospholipid syndrome (APS). The increase in tissue factor activity appears to be due to increased transcription and translation of nascent tissue factor molecules but is not due to de-encryption of existing tissue factor molecules on cells. Autoantibodies and/or immune complexes circulating in APS patients appear to enhance the expression of tissue factor activity on monocytes and endothelial cells. Anti-beta2-glycoprotein I (beta2GPI) autoantibodies have been specifically implicated in the antibody-mediated enhancement of tissue factor activity. The presence of antibodies against tissue factor pathway inhibitor (TFPI) in certain APS patients suggests that negative regulation of tissue factor activity might also be impaired in these patients. Given a mechanism involving increased tissue factor activity in APS-associated thrombosis, agents specifically targeting tissue factor activity may be a novel and efficacious therapy that is safer than current approaches to the management of APS.
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PMID:Mechanisms of autoantibody-induced monocyte tissue factor expression. 1550 69