Fibrinolysis and Proteolysis最新文献

{"title":"Oxidative stress induces urokinase-type plasminogen activator in RC-K8 human malignant lymphoma cells and H69 human small cell lung carcinoma cells","authors":"T. Miyazono, K. Niiya, T. Kiguchi, M. Minemura, T. Takahara, M. Harada, A. Watanabe","doi":"10.1054/FIPR.2000.0095","DOIUrl":"https://doi.org/10.1054/FIPR.2000.0095","url":null,"abstract":"Abstract Reactive oxygen species act as second messengers in the signal transduction induced by inflammatory stimuli such as interleukin-1 (IL-1), tumor necrosis factor-α (TNFα), and lipopolysaccharide (LPS). We have previously shown that both IL-1 and LPS induce the urokinase-type plasminogen activator (uPA) gene expression in RC-K8 human malignant lymphoma cells. Here, we provide evidence that an oxidative stimulation by eit her hydrogen peroxide (H2O2) or menadione (2-methyl-1,4-naphthoquinone (MQ)), a quinone compound that generates reactive oxygen species, causes the up-regulation of uPA expression in both RC-K8 cells and H69 human small cell lung carcinoma cells. uPA accumulation in their conditio ned media was significantly increased after treatment with H2O2or MQ and it was dose-dependent of the stimulus. Northern blotting analysis revealed that uPA mRNA levels in both RC-K8 and H69 cells were increased approximately 2-fold 9h after treatment with H2O2. The half-lives of uPA mRNA were not changed before and after H2O2stimulation. A synthetic antioxidant, N-acetylcysteine (NAC), completely inhibited the H2O2-induced uPA mRNA accumulation. The inhibition of the on-going protein synthesis by cycloheximide (CHX) did not inhibit the H2O2-induced uPA mRNA accumulation. These results suggest that the oxidative stress induces uPA accumulation through activating uPA gene transcription. Therefore, the stimuli that generate reactive oxygen species may influence many biological cell-functions mediated by the uPA/plasmin system by regulating uPA expression in malignant cells.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"32 1","pages":"366-373"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75994296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconstructing the interaction of glu-plasminogen with its receptor α-enolase","authors":"N.M. Andronicos ,&nbsp;M.S. Baker ,&nbsp;M. Lackmann ,&nbsp;M. Ranson","doi":"10.1054/fipr.2000.0090","DOIUrl":"https://doi.org/10.1054/fipr.2000.0090","url":null,"abstract":"<div><p><em>Objective</em>: Plasminogen binds with apparent low affinity to cell-surface receptors via its lysine binding sites. This enhances/stabilizes the activation-susceptible conformation. However, it is not known whether this lysine-mediated conformational change of plasminogen may affect its subsequent dissociation rate and hence its stability at the cell surface. Therefore, we sought to determine the relationship between the lysine-dependent conformation of plasminogen and its dissociation rate from its receptor.</p><p><em>Design</em>: BIACORE experiments were used to determine the kinetics of the interaction of glu-plasminogen with its receptor α-enolase. Intrinsic and extrinsic fluorescence spectroscopy were utilized to confirm if α-enolase induced a conformational change to glu-plasminogen as predicted by analyses of the BIACORE data.</p><p><em>Results</em>: The dissociation of glu-plasminogen from α-enolase was mediated by at least two components with apparent dissociation rate constants of k_d1= 4.7 × 10⁻²s⁻¹and k_d2= 1.6 × 10⁻³s⁻¹. This second slower dissociation event reflects an increase in the stability of the complex. Global analysis of the interaction suggested a two-state conformational change reaction, mediated by a concentration-dependent increase in the initial association rate constant. The apparent K_dpredicted by this analysis was 1μM. Fluorescence spectroscopy confirmed that α-enolase induced a more open conformation of glu-plasminogen.</p><p><em>Conclusions</em>: These results provide direct evidence that the binding of glu-plasminogen to α-enolase is not simply a low-affinity interaction, but involves a multivalent, competition binding reaction that is associated with a glu-plasminogen conformational change. This mechanism is compatible with the structure of glu-plasminogen. This has implications for the stability of binding and activation of glu-plasminogen at the cell surface.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 6","pages":"Pages 327-336"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71829148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Description of the plasminogen activating system in canine gingival crevicular fluid","authors":"P. Lindberg ,&nbsp;B. Kinnby ,&nbsp;I. Lecander ,&nbsp;L. Matsson","doi":"10.1054/fipr.2000.0091","DOIUrl":"https://doi.org/10.1054/fipr.2000.0091","url":null,"abstract":"<div><p>Summary <em>Objective</em>: Human gingival crevicular fluid (GCF) contains fibrinolytic activity, which has been suggested to be of significance for the etiology of periodontal diseases. We have previously found plasminogen activators (u-PA and t-PA) as well as PA inhibitors (PAI -1 and PAI-2) in human GCF and gingival tissues. The aim of this study was to evaluate the dog as an experimental animal for studying the fibrinolytic system (the plasminogen activating system) with available reagents and to describe the system in dog cr evicular fluid.</p><p><em>Design</em>: Six dogs were used. Samples from untreated gingival areas showing chronic gingivitis were collected with disks of Millipore filter. Fibrinolytic activity was assayed using a preformed fibrin gel in microtiter plates. t-PA as well as PAI-2 were assayed with ELISAs and Western blotting using antibodies against human antigens.</p><p><em>Results</em>: All samples showed fibrinolytic activity. The fibrinolytic activity could be completely quenched by antibodies against human t-PA. Antigen concentrations were similar to those found in humans; the median t-PA concentration in GCF from chronic gingivitis was 0.1μg/ml and the median PAI-2 concentration was 1.6μg/ml. Western blotting showed bands in the same kDa positions as for human t-PA and PAI-2. As in humans, both antibodies also revealed high-molecular-weight bands of similar size (130 kDa), which are likely to represent a complex between t-PA and PAI-2.</p><p><em>Conclusion</em>: Our results clearly show that the cross-reactivity is genuine and that these antibodies, developed against human antigens, can be used for experimental studies in the dog.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 6","pages":"Pages 337-342"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71829429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconstructing the interaction of glu-plasminogen with its receptor α-enolase","authors":"N. Andronicos, M. Baker, M. Lackmann, M. Ranson","doi":"10.1054/FIPR.2000.0090","DOIUrl":"https://doi.org/10.1054/FIPR.2000.0090","url":null,"abstract":"Abstract Objective: Plasminogen binds with apparent low affinity to cell-surface receptors via its lysine binding sites. This enhances/stabilizes the activation-susceptible conformation. However, it is not known whether this lysine-mediated conformational change of plasminogen may affect its subsequent dissociation rate and hence its stability at the cell surface. Therefore, we sought to determine the relationship between the lysine-dependent conformation of plasminogen and its dissociation rate from its receptor. Design: BIACORE experiments were used to determine the kinetics of the interaction of glu-plasminogen with its receptor α-enolase. Intrinsic and extrinsic fluorescence spectroscopy were utilized to confirm if α-enolase induced a conformational change to glu-plasminogen as predicted by analyses of the BIACORE data. Results: The dissociation of glu-plasminogen from α-enolase was mediated by at least two components with apparent dissociation rate constants of kd1= 4.7 × 10−2s−1and kd2= 1.6 × 10−3s−1. This second slower dissociation event reflects an increase in the stability of the complex. Global analysis of the interaction suggested a two-state conformational change reaction, mediated by a concentration-dependent increase in the initial association rate constant. The apparent Kdpredicted by this analysis was 1μM. Fluorescence spectroscopy confirmed that α-enolase induced a more open conformation of glu-plasminogen. Conclusions: These results provide direct evidence that the binding of glu-plasminogen to α-enolase is not simply a low-affinity interaction, but involves a multivalent, competition binding reaction that is associated with a glu-plasminogen conformational change. This mechanism is compatible with the structure of glu-plasminogen. This has implications for the stability of binding and activation of glu-plasminogen at the cell surface.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"72 1","pages":"327-336"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85392822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress induces urokinase-type plasminogen activator in RC-K8 human malignant lymphoma cells and H69 human small cell lung carcinoma cells","authors":"T. Miyazono ,&nbsp;K. Niiya ,&nbsp;T. Kiguchi ,&nbsp;M. Minemura ,&nbsp;T. Takahara ,&nbsp;M. Harada ,&nbsp;A. Watanabe","doi":"10.1054/fipr.2000.0095","DOIUrl":"https://doi.org/10.1054/fipr.2000.0095","url":null,"abstract":"<div><p>Reactive oxygen species act as second messengers in the signal transduction induced by inflammatory stimuli such as interleukin-1 (IL-1), tumor necrosis factor-α (TNFα), and lipopolysaccharide (LPS). We have previously shown that both IL-1 and LPS induce the urokinase-type plasminogen activator (uPA) gene expression in RC-K8 human malignant lymphoma cells. Here, we provide evidence that an oxidative stimulation by eit her hydrogen peroxide (H₂O₂) or menadione (2-methyl-1,4-naphthoquinone (MQ)), a quinone compound that generates reactive oxygen species, causes the up-regulation of uPA expression in both RC-K8 cells and H69 human small cell lung carcinoma cells. uPA accumulation in their conditio ned media was significantly increased after treatment with H₂O₂or MQ and it was dose-dependent of the stimulus. Northern blotting analysis revealed that uPA mRNA levels in both RC-K8 and H69 cells were increased approximately 2-fold 9h after treatment with H₂O₂. The half-lives of uPA mRNA were not changed before and after H₂O₂stimulation. A synthetic antioxidant, N-acetylcysteine (NAC), completely inhibited the H₂O₂-induced uPA mRNA accumulation. The inhibition of the on-going protein synthesis by cycloheximide (CHX) did not inhibit the H₂O₂-induced uPA mRNA accumulation. These results suggest that the oxidative stress induces uPA accumulation through activating uPA gene transcription. Therefore, the stimuli that generate reactive oxygen species may influence many biological cell-functions mediated by the uPA/plasmin system by regulating uPA expression in malignant cells.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 6","pages":"Pages 366-373"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71829427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid detection of streptokinase resistance using a bedside lytic assay of dry reagent technology","authors":"K. Al Shwafi ,&nbsp;A. de Meester ,&nbsp;B. Pirenne ,&nbsp;J. Renkin ,&nbsp;J. Col","doi":"10.1054/fipr.2000.0094","DOIUrl":"https://doi.org/10.1054/fipr.2000.0094","url":null,"abstract":"<div><p>A new bedside lytic assay using dry reagent technology for rapid (3–5 min) detection of streptokinase resistance (SKR) was recently introduced, which measures lysis onset time (LOT) of whole blood clot in response to high and low streptokinase (SK) concentrations: 100 U/ml (SK100) and 10 U/ml (SK10). SKR was defined by pro longation of LOT, previously correlated with the standard SK Reactivity Test and with clinical outcome of acute myocardial infarction (AMI) SK-treated patients, high SKR when SK100 &gt; 50 seconds and SK10 &gt; 120 seconds; partial SKR when SK10 &gt; 120 seconds. Five prospective clinical groups (325 patients) were screened in cardiac units of four university hospitals. In patients previously treated with SK, the prevalence of SKR was 87% (70% high, 17% partial); in those who had documented streptoco ccal infection, 92% (75% high, 17% partial); and in patients with rheumatic heart disease, 76% (all high). SKR prevalence was 55% (33% high, 22% partial) in those with recent respiratory tract infection. In 225 acute coronary patients, SKR was 28% (21% h igh, 7% partial), and was identical by gender, but was 36% (32% high, 4% partial) in patients ≥ 65 years versus 19% (9% high, 10% partial) in those ≤ 65 years (<em>P</em>&lt; 0.0001).</p><p>In conclusion, we demonstrated (with a rapid functional assay) the consistence of our results with the expected prevalence of SKR in the groups studied, this points out to the feasibility of pre-therapeutic detection of SKR and choice between t-PA and SK made at bedside without delaying the onset of treatment. As SKR is common among candidates for thrombolysis, pre-therapeutic detection of SKR merits further investigation.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 6","pages":"Pages 351-357"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71829430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Description of the plasminogen activating system in canine gingival crevicular fluid","authors":"P. Lindberg, B. Kinnby, I. Lecander, L. Matsson","doi":"10.1054/FIPR.2000.0091","DOIUrl":"https://doi.org/10.1054/FIPR.2000.0091","url":null,"abstract":"Abstract Summary Objective : Human gingival crevicular fluid (GCF) contains fibrinolytic activity, which has been suggested to be of significance for the etiology of periodontal diseases. We have previously found plasminogen activators (u-PA and t-PA) as well as PA inhibitors (PAI -1 and PAI-2) in human GCF and gingival tissues. The aim of this study was to evaluate the dog as an experimental animal for studying the fibrinolytic system (the plasminogen activating system) with available reagents and to describe the system in dog cr evicular fluid. Design : Six dogs were used. Samples from untreated gingival areas showing chronic gingivitis were collected with disks of Millipore filter. Fibrinolytic activity was assayed using a preformed fibrin gel in microtiter plates. t-PA as well as PAI-2 were assayed with ELISAs and Western blotting using antibodies against human antigens. Results : All samples showed fibrinolytic activity. The fibrinolytic activity could be completely quenched by antibodies against human t-PA. Antigen concentrations were similar to those found in humans; the median t-PA concentration in GCF from chronic gingivitis was 0.1μg/ml and the median PAI-2 concentration was 1.6μg/ml. Western blotting showed bands in the same kDa positions as for human t-PA and PAI-2. As in humans, both antibodies also revealed high-molecular-weight bands of similar size (130 kDa), which are likely to represent a complex between t-PA and PAI-2. Conclusion : Our results clearly show that the cross-reactivity is genuine and that these antibodies, developed against human antigens, can be used for experimental studies in the dog.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"457 1","pages":"337-342"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82973815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consequences of inhibition of plasma carboxypeptidase B on in vivo thrombolysis, thrombosis and hemostasis","authors":"C.J. Refino ,&nbsp;L. DeGuzman ,&nbsp;D. Schmitt ,&nbsp;R. Smyth ,&nbsp;S. Jeet ,&nbsp;M.T. Lipari ,&nbsp;D. Eaton ,&nbsp;S. Bunting","doi":"10.1054/fipr.2000.0087","DOIUrl":"https://doi.org/10.1054/fipr.2000.0087","url":null,"abstract":"<div><p>To further evaluate the role of plasma carboxypeptidase B (pCPB) in modulating fibrinolysis, we investigated the effects of inhibiting pCPB on tissue plasminogen activator (tPA) induced lysis of preformed whole blood clots and on thrombus formation in vivo. In a rabbit arterio-venous shunt model we observed that a systemic administration of potato carboxypeptidase inhibitor (PCI), an inhibitor of pCPB, accelerated the rate of clot lysis induced by therapeutic concentrations of tPA. This effect was equivalent to increasing the relative potency of tPA by more than a factor of two and was achieved even when PCI was administered systemically in the presence of heparin. The effect of pCPB inhibition on thrombus formation was evaluated in a novel rabbit model of venous thrombosis. In this model, systemic administration of PCI reduced thrombus weight to 33% of saline treated controls. However, this regimen resulted in a modest bleeding tendency, comparable to that seen in rabbits treated with an antithrombotic regimen of heparin. Taken together, these data further support the hypothesis that pCPB’s function is to attenuate fibrinolysis and may thereby play a role in hemostasis following vascular injury.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 5","pages":"Pages 305-314"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71828584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased synthesis of tissue plasminogen activator antigen in users of oral contraceptives","authors":"K.R. Petersen ,&nbsp;M. Jørgensen ,&nbsp;N. Vinberg ,&nbsp;J. Gram ,&nbsp;S.O. Skouby ,&nbsp;K.H. Tønnesen ,&nbsp;J. Jespersen","doi":"10.1054/fipr.2000.0089","DOIUrl":"https://doi.org/10.1054/fipr.2000.0089","url":null,"abstract":"<div><p><em>Objective:</em> To study why the plasma antigen concentrations of tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) are reduced in users of oral contraceptives (OCs).</p><p><em>Design:</em>Open, non-randomized study.</p><p><em>Setting:</em> University departments in Copenhagen and Esbjerg, Denmark.</p><p><em>Subjects:</em> Sixteen healthy female volunteers between 21 and 32 years of age. Eight women used an OC containing ethinyl estradiol and gestodene (OC group) and eight women used non-hormonal contraception (control group).</p><p><em>Intervention:</em> Determination of splanchnic plasma flow and total plasma volume; measurement of t-PA and PAI-1 antigen as well as active t-PA and PAI-1 in plasma from an artery and a liver vein</p><p><em>Main outcome measures:</em>Extraction, clearance, net rate of catabolism and mean transit time of t-PA and PAI-1 in the splanchnic circulation.</p><p><em>Results:</em> Arterial plasma concentrations of t-PA and PAI-1 antigen were reduced in the OC group whereas the concentrations of active t-PA and active PAI-I were similar. The arterio-venous (A-V) difference for t-PA antigen and active t-PA was positive in both groups. The net splanchnic catabolism of t-PA antigen was reduced in the OC group, while the extraction, clearance and mean transit time were similar. The extraction, clearance, net rate of catabolism and mean transit time of active t-PA did not differ between the two groups. For PAI-1, differences in the main outcome measures between the two groups could not be determined, as there was no statistically significant A-V difference for PAI-1 antigen in any of the groups and a significant A-V difference for active PAI-1 in the control group only.</p><p><em>Conclusion:</em> The reduced net splanchnic catabolism of t-PA antigen in the OC users probably reflects a decreased peripheral synthesis of t-PA, which may explain the low plasma concentration in these women. The mechanism underlying the reduced concentration of PAI-1 antigen in the OC users could not be determined by the present methodology.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 5","pages":"Pages 315-321"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71828587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consequences of inhibition of plasma carboxypeptidase B on in vivo thrombolysis, thrombosis and hemostasis","authors":"C. Refino, L. Deguzman, D. Schmitt, R. Smyth, S. Jeet, M. Lipari, D. Eaton, S. Bunting","doi":"10.1054/FIPR.2000.0087","DOIUrl":"https://doi.org/10.1054/FIPR.2000.0087","url":null,"abstract":"Abstract To further evaluate the role of plasma carboxypeptidase B (pCPB) in modulating fibrinolysis, we investigated the effects of inhibiting pCPB on tissue plasminogen activator (tPA) induced lysis of preformed whole blood clots and on thrombus formation in vivo. In a rabbit arterio-venous shunt model we observed that a systemic administration of potato carboxypeptidase inhibitor (PCI), an inhibitor of pCPB, accelerated the rate of clot lysis induced by therapeutic concentrations of tPA. This effect was equivalent to increasing the relative potency of tPA by more than a factor of two and was achieved even when PCI was administered systemically in the presence of heparin. The effect of pCPB inhibition on thrombus formation was evaluated in a novel rabbit model of venous thrombosis. In this model, systemic administration of PCI reduced thrombus weight to 33% of saline treated controls. However, this regimen resulted in a modest bleeding tendency, comparable to that seen in rabbits treated with an antithrombotic regimen of heparin. Taken together, these data further support the hypothesis that pCPB’s function is to attenuate fibrinolysis and may thereby play a role in hemostasis following vascular injury.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"45 1","pages":"305-314"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82838122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}