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Tatsuya Atsumi

Publications and source records attributed to Tatsuya Atsumi.

At least 19 recordsLinked to original sources
PubMed2024

Muscle Tissue Transcriptome of Idiopathic Inflammatory Myopathy Reflects the Muscle Damage Process by Monocytes and Presence of Skin Lesions.

OBJECTIVE: We aim to investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM). METHODS: Bulk RNA-sequencing was performed on muscle biopsy samples from 16 patients with dermatomyositis (DM) and 9 patients with polymyositis (PM). Seven tested positive for anti-aminoacyl transfer RNA synthetase antibodies in the patients with DM (ARS-DM). We conducted weighted gene coexpression network analysis (WGCNA), differentially expressed gene (DEG) analysis, and gene set variation analysis to assess contributions of specific pathways. Cell proportions in muscle specimens were estimated using a deconvolution approach. RESULTS: WGCNA revealed significant positive correlations between serum creatine kinase (CK) levels and gene modules involved in cellular respiration, phagocytosis, and oxidative phosphorylation (OXPHOS). Significant positive correlations were also observed between CK levels and proportions of CD16-positive and negative monocytes and myeloid dendritic cells. Notably, patients with DM demonstrated enrichment of complement and interferon-α and γ pathway genes compared with those with PM. Furthermore, ARS-DM demonstrated a higher proportion of Th1 cells and DEGs related to OXPHOS. Additionally, serum Krebs von den Lungen-6 levels correlated with gene modules associated with extracellular matrix and the transforming growth factor-β signaling pathway. CONCLUSION: Our study highlights a significant involvement of monocytes in muscle damage and delineates pathologic differences among IIM subtypes. DM was characterized by complement and interferon-α and γ signaling, whereas ARS-DM was associated with OXPHOS. Distinctive gene expression variations in muscle specimens suggest that different pathologic mechanisms underlie muscle damage in each IIM phenotype.

Humans↗
PubMed2006

[Phosphatidylserine-dependent anti-prothrombin antibody as a new marker for the diagnosis of antiphospholipid syndrome].

Antiphospholipid syndrome (APS) is an autoimmune disorder in which vascular thrombosis and recurrent pregnancy loss occur in patients with antiphospholipid antibodies(aPL). Measurements of the beta2-glycoprotein I-dependent anticardiolipin antibody(aCL) and lupus anticoagulant(LAC) are the only laboratory tests available for the diagnosis of APS. Recently, phosphatidylserine-dependent antiprothrombin antibody(aPS/PT) has been detected. aPS/PT was measured by ELISA using the phosphatidylserine-prothrombin complex as an antigen immobilized on ELISA plates in the presence of CaCl2. In our study of 219 patients with APS and autoimmune diseases, the prevalence of aPS/PT-IgG in those with APS was 42.2%, which was significantly higher than that(4.6%) in patients with autoimmune diseases. Furthermore, aPS/PT was closely associated with APS manifestations with an odds ratio (OR) of 2.92 (95% confidence interval (95% CI): 1.33 to approximately 6.40), whereas the OR for aCL was 2.06 (95% CI: 0.91 to approximately 4.66). In addition, aPS/PT-IgG was strongly correlated with the presence of LAC as detected with a diluted Russell viper venom time test (dRVVT) (OR: 38.2, 95% CI: 13.4 to approximately 109.1). The monoclonal antibody (23-1D) of aPS/PT also prolonged the clotting time in LAC tests (aPTT, dRVVT, and kaolin clotting time) in a concentration-dependent manner. In conclusion, aPS/PT is more closely associated with manifestations of APS and LAC, and positive results from an aPS/PT test can mark thrombotic events in APS patients. The determination of aPS/PT in clinical practice, in conjunction with that of other aPL, may improve the likelihood of recognizing APS.

Abortion, Habitual↗
PubMed2005

Pathogenesis of antiphospholipid antibodies: impairment of fibrinolysis and monocyte activation via the p38 mitogen-activated protein kinase pathway.

Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis or pregnancy morbidity associated with antiphospholipid antibodies (aPL). Impaired fibrinolysis is a contributing factor for the development of thrombosis, and the effect of aPL in the fibrinolytic system has been investigated. Impaired release of tPA and enhanced release of PAI-1 after endothelial activation is reported in patients with APS. Elevated Lipoprotein (a) levels have been found in APS, which results in inhibition of fibrinolytic activity. Phospholipid-bound beta(2)-glycoprotein I (beta(2)GPI) is a major autoantigen for aPLs. beta(2)GPI exerts both anti-coagulant and pro-coagulant properties mainly by interacting with other phospholipid-binding proteins such as coagulation factors and protein C. Dramatic increase in the affinity of beta(2)GPI to the cell surface is induced by binding of pathogenic anti-beta(2)GPI antibodies, which may modify the physiological function of beta(2)GPI and may affect the coagulation/fibrinolysis balance on the cell surface. Using chromogenic assays for measuring fibrinolytic activity, we demonstrated that addition of monoclonal anticardiolipin antibody (aCL) decreases the activity of extrinsic/intrinsic fibrinolysis. Significantly lower activity of intrinsic fibrinolysis was also demonstrated in the euglobulin fractions from APS patients. Endothelial cells and monocytes are activated by aPLs in vitro, resulting in production of tissue factor (TF), a major initiator of the coagulation system. Recently, aPLs are reported to induce thrombocytes to produce thromboxane. The importance of apoE receptor 2 on platelets for the binding of artificially dimerized beta(2)GPI was suggested. By investigating aPL-inducible genes in peripheral blood mononuclear cells, we found that the mitogen-activated protein kinase (MAPK) pathway was up-regulated. Using a monocyte cell line, phosphorylation of p38 MAPK, NF-kappaB translocation to the nuclear fraction, and up-regulated TF mRNA expression were demonstrated after treatment with monoclonal aCL. These phenomena were observed only in the presence of beta(2)GPI. Moreover, a specific p38 MAPK inihibitor SB203580 decreased aCL/beta(2)GPI-induced TF mRNA expression. Thus, aCL/beta(2)GPI plays dual roles in the pathogenesis of APS, firstly by deranging the fibrinolytic system and secondly by activating monocytes, endothelial cells and thrombocytes to produce TF or thromboxane.

Antibodies, Antiphospholipid↗
PubMed2005

Antigenic structures recognized by anti-beta2-glycoprotein I auto-antibodies.

Beta2-glycoprotein I (beta2-GPI) is a major antigen for anti-cardiolipin antibodies and their epitopes are cryptic. Conformation of each domain of beta2-GPI was optimized from its crystal structure by energy minimization and by molecular dynamics simulation. Three electrostatic interactions, i.e. D193-K246, D222-K317 and E228-K308, were observed between domains IV and V in the optimized structure that was constructed based on the consensus sequences obtained by the phage-displayed random peptide library. Antigenic structures determined by the epitope mapping mainly consisted of hydrophobic amino acids located on two discontinuous sequences in domain IV. These amino acid clusters, as an epitope, were covered by domain V and were of a hidden nature. A similar but incomplete counterpart to the epitopic clusters was found in domain I but was not in domains II or III. Binding of anti-beta2-GPI auto-antibodies to solid-phase beta2-GPI was significantly reduced either by L replacement for W235, a common amino acid component for the epitopes, or by V replacement for all of D193, D222 and E228. Structural analysis indicated a hypothesis that these electrostatic interactions between domains IV and V retained exposure to W235 and that epitope spreading occurred in the region surrounding W235. Thus, epitopic structures recognized by anti-beta2-GPI auto-antibodies are cryptic and inter-domain electrostatic interactions are involved in their in exposure.

Amino Acid Substitution↗
PubMed2005

Significance of valine/leucine247 polymorphism of beta2-glycoprotein I in antiphospholipid syndrome: increased reactivity of anti-beta2-glycoprotein I autoantibodies to the valine247 beta2-glycoprotein I variant.

OBJECTIVE: To clarify the consequences of the valine/leucine polymorphism at position 247 of the beta(2)-glycoprotein I (beta(2)GPI) gene in patients with antiphospholipid syndrome (APS), by investigating the correlation between genotypes and the presence of anti-beta(2)GPI antibody. The reactivity of anti-beta(2)GPI antibodies was characterized using recombinant Val(247) and Leu(247) beta(2)GPI. METHODS: Sixty-five Japanese patients with APS and/or systemic lupus erythematosus who were positive for antiphospholipid antibodies and 61 controls were analyzed for the presence of the Val/Leu(247) polymorphism of beta(2)GPI. Polymorphism assignment was determined by polymerase chain reaction followed by restriction enzyme digestion. Recombinant Val(247) and Leu(247) beta(2)GPI were established to compare the reactivity of anti-beta(2)GPI antibodies to beta(2)GPI between these variants. The variants were prepared on polyoxygenated plates or cardiolipin-coated plates, and the reactivity of a series of anti-beta(2)GPI antibodies (immunized anti-human beta(2)GPI monoclonal antibodies [Cof-19-21] and autoimmune anti-beta(2)GPI monoclonal antibodies [EY1C8, EY2C9, and TM1G2]) and IgGs purified from patient sera was investigated. RESULTS: A positive correlation between the Val(247) allele and the presence of anti-beta(2)GPI antibodies was observed in the patient group. Human monoclonal/polyclonal anti-beta(2)GPI autoantibodies showed higher binding to recombinant Val(247) beta(2)GPI than to Leu(247) beta(2)GPI, although no difference in the reactivity of the immunized anti-beta(2)GPI between these variants was observed. Conformational optimization showed that the replacement of Leu(247) by Val(247) led to a significant alteration in the tertiary structure of domain V and/or the domain IV-V interaction. CONCLUSION: The Val(247) beta(2)GPI allele was associated with both a high frequency of anti-beta(2)GPI antibodies and stronger reactivity with anti-beta(2)GPI antibodies compared with the Leu(247) beta(2)GPI allele, suggesting that the Val(247) beta(2)GPI allele may be one of the genetic risk factors for development of APS.

Adult↗
PubMed2005

Butyrate suppresses tumor necrosis factor alpha production by regulating specific messenger RNA degradation mediated through a cis-acting AU-rich element.

OBJECTIVE: To study the capacity of butyrate to inhibit production of tumor necrosis factor alpha (TNFalpha) in macrophage-like synoviocytes (MLS) from patients with rheumatoid arthritis (RA), in human peripheral monocytes, and in murine RAW264.7 macrophages. METHODS: The concentrations of TNFalpha in culture supernatants of these cells were measured using enzyme-linked immunosorbent assay. The expression levels of various messenger RNAs (mRNA), such as those for TNFalpha, the mRNA-binding protein TIS11B, and luciferase, were measured using real-time quantitative polymerase chain reaction. The in vitro effects of butyrate on transcriptional regulation were evaluated by transfection with various reporter plasmids in RAW264.7 macrophages. The effects of TIS11B on TNFalpha expression were examined using an overexpression model of TIS11B in RAW264.7 cells. RESULTS: Butyrate suppressed TNFalpha protein and mRNA production in MLS and monocytes, but paradoxically enhanced transactivation of the TNFalpha promoter. Expression of the AU-rich element (ARE)-binding protein TIS11B was up-regulated by butyrate. Induction of TNFalpha mRNA by lipopolysaccharide was significantly inhibited when TIS11B was overexpressed. Butyrate facilitated the degradation of luciferase transcripts containing the 3'-untranslated region (3'-UTR) of TNFalpha, and this effect was dependent on the ARE in the 3'-UTR that is known to be involved in the regulation of mRNA degradation. CONCLUSION: These results indicate that butyrate suppresses TNFalpha expression by facilitating mRNA degradation mediated through a cis-acting ARE. Butyrate has the ability to regulate TNFalpha at the mRNA level and is therefore a potential therapeutic drug for RA patients.

3' Untranslated Regions↗
PubMed2005

Research around beta 2-glycoprotein I: a major target for antiphospholipid antibodies.

Beta2-glycoprotein I (beta2GPI), a phospholipid-binding protein, is one of the major target antigens for antiphospholipid antibodies (aPL) found in patients with antiphospholipid syndrome (APS). Thrombophilic disorders in APS patients are strongly associated with aPL, and their pathogenic properties depend on the presence of beta2GPI. Procoagulant cell stimulation by aPL, via beta2GPI, is one of the most plausible mechanisms of thrombosis in APS, and p38 mitogen activated protein kinase (MAPK) pathway plays a crucial role in such activation. beta2GPI is proteolytically cleaved in domain V by activated factor X or plasmin, leading to the generation of the nicked form of beta2GPI. Recently, increasing attention is focused on the role of nicked-beta2GPI as a regulator of extrinsic fibrinolysis pathway.

Amino Acid Sequence↗
PubMed2005

Antiprothrombin antibodies detected in two different assay systems. Prevalence and clinical significance in systemic lupus erythematosus.

We evaluated the clinical significance of aPT and aPS-PT by testing for the presence of these antibodies in 212 SLE patients and in 100 healthy individuals. Results show that anti-prothrombin antibodies were found in 47% of the patients (aPT in 31% and aPS-PT in 31%). Their presence did not correlate with that of aCL, anti-beta2GPI, LA and/or anti-protein S. IgG but not IgM aPT were more frequently found in patients with thrombosis than in those without. IgG and IgM aPS-PT were also more frequent in patients with thrombosis (venous and/or arterial) than in those without. Levels of IgG aPT and IgG and IgM aPS-PT were higher in patients with thrombosis than in those without. Although aPT and aPS-PT were more frequently found in women with adverse obstetric history than in those without, the differences were not statistically significant. More significantly, 48% of the patients with aPL-related clinical features who were negative for standard tests had antiprothrombin antibodies. We can conclude that aPT and aPS-PT are frequently found in SLE. Their presence is associated with thrombosis, making these antibodies potential markers for the APS. Testing for these antibodies could be of clinical benefit in patients who are negative for the routinely used tests.

Adult↗
PubMed2005

Vertebral fracture and bone mineral density in women receiving high dose glucocorticoids for treatment of autoimmune diseases.

OBJECTIVE: To evaluate the factors influencing the occurrence of vertebral fracture in patients receiving high dose glucocorticoids (GC). METHODS: A cross-sectional study was performed on women who had received at least 0.5 mg/kg of oral glucocorticoid for the treatment of autoimmune diseases for more than 1 month between 1998 and 2003. Logistic regression analysis and chi-square test were used to examine the effects of glucocorticoid dose and other factors on vertebral fractures. Receiver-operating characteristics curve (ROC) analysis was used to determine the bone mineral density (BMD) cutoff value for the risk of vertebral fracture. RESULTS: The study population comprised 160 women, including 35 with vertebral fractures. In ROC analysis, the BMD threshold of the risk of fracture for postmenopausal women (0.787 g/cm2 , T score -2.1) was lower than that for premenopausal women (0.843 g/cm2 , T score -1.7). Among patients with fractures, 7 of 16 premenopausal patients had normal BMD values (T score > -1), whereas only one of 19 postmenopausal patients showed a comparable level of BMD. Additionally, vertebral fracture was more frequent for patients with high total cholesterol values (> 280 mg/dl) than for those with normal total cholesterol values (< 220 mg/dl). Moreover, patients with high total cholesterol values had lower BMD values than those with normal total cholesterol values. CONCLUSION: The fact that vertebral fracture frequently occurred in premenopausal patients with normal BMD and evidence that hyperlipidemia correlated with fracture suggest the pathology of vertebral fracture secondary to high dose glucocorticoid therapy is multifactorial and possibly involves lipid metabolism.

Adolescent↗
PubMed2004

The p38 mitogen-activated protein kinase (MAPK) pathway mediates induction of the tissue factor gene in monocytes stimulated with human monoclonal anti-beta2Glycoprotein I antibodies.

The anti-phospholipid syndrome (APS) is characterized by thrombosis and the presence of anti-phospholipid antibodies (aPL). Tissue factor (TF), the major initiator of the coagulation system, is induced on monocytes by aPL in vitro, explaining, in part, the pathophysiology in this syndrome. However, little is known regarding the nature of the aPL-induced signal transduction pathways leading to TF expression. In this study, we investigated aPL-inducible genes in PBMC using cDNA array system and real-time PCR. Our results indicated that the mitogen-activated protein kinase (MAPK) pathway was related to TF expression when PBMCs were treated, in the presence of beta(2)Glycoprotein I (beta(2)GPI), with human monoclonal anti-beta(2)GPI antibodies [beta(2)GPI-dependent anti-cardiolipin antibodies (aCL/beta(2)GPI)]. Western blotting studies using monocyte cell line (RAW264.7) demonstrated that p38 MAPK protein was phosphorylated with nuclear factor kappaB (NF-kappaB) activation by monoclonal aCL/beta(2)GPI treatment, and that SB203580, a specific p38 MAPK inhibitor, decreased the aCL/beta(2)GPI-induced TF mRNA expression. The p38 MAPK phosphorylation, NF-kappaB translocation and TF mRNA expression triggered by aCL/beta(2)GPI were abolished in the absence of beta(2)GPI. These results demonstrated that the p38 MAPK signaling pathway plays an important role in aPL-induced TF expression on monocytes and suggest that the p38 MAPK may be a possible therapeutic target to modify a pro-thrombotic state in patients with APS.

Antibodies, Monoclonal↗
PubMed2004

Diagnostic value of antiagalactosyl IgG antibodies in rheumatoid arthritis.

Our objective in this study was to explore the diagnostic value of antiagalactosyl IgG antibodies in rheumatoid arthritis (RA). The study comprised 266 Japanese patients with systemic autoimmune diseases, including 60 with RA. Human agalactosyl IgG was prepared enzymatically, and the serum levels of antiagalactosyl IgG antibodies were determined using a lectin enzyme immunoassay. Serum IgG and IgM rheumatoid factors (RF) were measured using laser nephelometry for IgM (LN-RF) and an enzyme-linked immunosorbent assay for IgG (IgG-RF). Antiagalactosyl IgG antibodies were significantly more common in patients with RA than in those without (78% vs. 18%, odds ratio (OR) 16.51, 95% confidence interval (CI) 8.12-33.58, p<0.0001). Patients with RA also had a higher frequency of LN-RF than those without RA (75% vs. 28%, OR 7.81, 95% CI 3.91-15.58, p< 0.001). The specificity of antiagalactosyl IgG antibodies for RA was significantly higher than that of LN-RF (82% vs. 72%, p<0.0011). There was a significant correlation between titers of antiagalactosyl IgG antibodies and C-reactive protein levels. Antiagalactosyl IgG antibodies are more specific markers for RA than conventional LN-RF, and may provide useful information for the diagnosis of RA.

Antibodies↗
PubMed2004

Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a complex multigenic disease, is a typical antibody-mediated autoimmune disease characterized by production of autoantibodies against a variety of autoantigens and immune complex-type tissue inflammation, most prominently in the kidney. Evidence suggests that genetic factors predisposing to aberrant proliferation/maturation of self-reactive B cells initiate and propagate the disease. In SLE-prone New Zealand Black (NZB) mice and their F1 cross with New Zealand White (NZW) mice, B cell abnormalities can be ascribed mainly to self-reactive CD5+ B1 cells. Our genome-wide scans to search for susceptibility genes for aberrant activation of B1 cells in these mice showed evidence that the gene, Ltk, encoding leukocyte tyrosine kinase (LTK), is a possible candidate. LTK is a receptor-type protein tyrosine kinase, belonging to the insulin receptor superfamily, and is mainly expressed in B lymphocyte precursors and neuronal tissues. Sequence and functional analyses of the gene revealed that NZB has a gain-of-function polymorphism in the LTK kinase domain near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase (PI3K). SLE patients also had this type of Ltk polymorphism with a significantly higher frequency compared with the healthy controls. Our findings suggest that these polymorphic LTKs cause up-regulation of the PI3K pathway and possibly form one genetic component of susceptibility to abnormal proliferation of self-reactive B cells in SLE.

Adult↗
PubMed2004

Nicked beta2-glycoprotein I: a marker of cerebral infarct and a novel role in the negative feedback pathway of extrinsic fibrinolysis.

BEta(2)-glycoprotein I (beta(2)-GPI) is proteolytically cleaved by plasmin in domain V (nicked beta(2)-GPI), being unable to bind to phospholipids. This cleavage may occur in vivo and elevated plasma levels of nicked beta(2)-GPI were detected in patients with massive plasmin generation and fibrinolysis turnover. In this study, we report higher prevalence of elevated ratio of nicked beta(2)-GPI against total beta(2)-GPI in patients with ischemic stroke (63%) and healthy subjects with lacunar infarct (27%) when compared to healthy subjects with normal findings on magnetic resonance imaging (8%), suggesting that nicked beta(2)-GPI might have a physiologic role beyond that of its parent molecule in patients with thrombosis. Several inhibitors of extrinsic fibrinolysis are known, but a negative feedback regulator has not been yet documented. We demonstrate that nicked beta(2)-GPI binds to Glu-plasminogen with K(D) of 0.37 x 10(-6) M, presumably mediated by the interaction between the fifth domain of nicked beta(2)-GPI and the fifth kringle domain of Glu-plasminogen. Nicked beta(2)-GPI also suppressed plasmin generation up to 70% in the presence of tissue plasminogen activator, plasminogen, and fibrin. Intact beta(2)-GPI lacks these properties. These data suggest that beta(2)-GPI/plasmin-nicked beta(2)-GPI controls extrinsic fibrinolysis via a negative feedback pathway loop.

Aged↗
PubMed2004

Antiprothombin antibodies and the diagnosis of antiphospholipid syndrome.

The preliminary classification criteria for definite antiphospholipid syndrome (APS) include the presence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA) as laboratory criteria. However, antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies comprising also antibodies against phospholipid-binding proteins or their complexes with phospholipids. Prothrombin is one of the antigen recognized by aPL. In the last decade, there has been increasing interest in antibodies against prothrombin alone and those against phosphatidylserine-prothrombin complex. The latter, phosphatidylserine-dependent antiprothrombin antibodies (aPT), have been closely associated with APS and LA. In this paper, we review the properties of antiprothrombin antibodies.

Animals↗
PubMed2004

Phosphatidylserine-dependent antiprothrombin antibodies are not useful markers for high-risk women with recurrent miscarriages.

To determine the possible association between antiprothrombin antibodies and conventional antiphospholipid antibody (aPL) 1 (1.0%), 2 (2.0%) and 17 (17.0%) were found to be positive for phosphatidylserine-dependent antiprothrombin antibody (aPS/PT) IgG, beta2glycoprotein I-dependent anticardiolipin antibody, and lupus anticoagulant by activated partial thromboplastin time (LA), respectively, in 100 recurrent aborters. Because patients with aPS/PT were included in the 17 with LA, we should not add aPS/PT measurement to routine testing in addition to conventional aPL for patients with recurrent miscarriage.

Abortion, Habitual↗
PubMed2004

Beta2-glycoprotein I, anti-beta2-glycoprotein I, and fibrinolysis.

Beta2-glycoprotein-I (beta2GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. Beta2GPI has been known as a natural anticoagulant regulator. Beta2GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, beta2GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, beta2GPI may contribute to thrombin generation in vivo. Phospholipid-bound beta2GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-beta2GPI antibodies increases the affinity of beta2GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of beta2GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-beta2GPI antibodies with beta2GPI also decreased fibrinolytic activity in this assay system. beta2GPI is proteolytically cleaved by plasmin in domain V (nicked beta2GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked beta2GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked beta2GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop.

Animals↗