Fibrinolysis最新文献

{"title":"Plasminogen activator inhibitor 2 in menstrual endometrium and in primary cultures of endometrial cells","authors":"J. Nordengren,&nbsp;B. Casslén,&nbsp;I. Lecander","doi":"10.1016/S0268-9499(96)80010-5","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80010-5","url":null,"abstract":"<div><p>The objective was to study content, distribution, and cyclic variation of plasminogen activator inhibitor 2 (PAI-2) in human endometrial tissue and secretion. Regulation of PAI-2 by steroid hormones and growth factor was further studied in primary cultures of endometrial cells.</p><p>Endometrial secretion and menstrual discharge was obtained from healthy volunteers, and endometrial tissue from patients at operation. PAI-2 was assayed with an ELISA in endometrial section, menstrual discharge, tissue homogenates, and conditioned media. Furthermore, endometrial tissue was analyzed with immuno-histochemistry.</p><p>PAI-2 was found in very low concentrations in extracts of normal non-pregnant human endometrium, and was released to the uterine cavity in small quantities without any difference between the proliferative and secretory phases. Also, no specific immuno-staining for PAI-2 was seen in the proliferative and secretory phases. However, in menstrual endometrium certain cells in the stroma stained positive for PAI-2, and the concentration of PAI-2 was high in menstrual blood.</p><p>Endometrial cells obtained in the proliferative, as well as in the secretory phases, contained significant amounts of PAI-2 after three days culture. A minor fraction was released from the stromal cells, but not from the epithelial cells. Intracellular PAI-2 was in its low molecular weight form, while both the low and high molecular weight forms were secreted in stromal cell cultures. Treatment of the cell cultures with estradiol, progesterone, DH-testosterone, epidermal growth factor, transforming growth factor α, and basic fibroblast growth factor affected neither the content nor the release of PAI-2.</p><p>Significant levels of PAI-2 were associated only with the menstrual phase in vivo, whereas cultured endometrial cells, obtained in the proliferative and secretory phases, expressed PAI-2. Thus, PAI-2 production in primary cultures of endometrial cells seems to be an in vitro phenomenon.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 295-302"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80010-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71863696","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":"Regulation of the secretion of urokinase-type plasminogen activator and type-1 plasminogen activator inhibitor in T98G human glioblastoma cells by cytokines and dexamethasone","authors":"E. Yoshida ,&nbsp;S. Ohmura ,&nbsp;J. Kawano ,&nbsp;M. Sugiki ,&nbsp;H.C. Kwaan ,&nbsp;M. Maruyama","doi":"10.1016/S0268-9499(96)80011-7","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80011-7","url":null,"abstract":"<div><p>The plasminogen-plasmin system plays an important role in regulating tumor invasion, tissue remodelling, and neovascularization. We investigated the effect of various cytokines on fibrinolytic activity produced by T98G glioblastoma cells. The cytokines used were interleukin (IL)-1α, and β, IL-2, IL-3, IL-4, IL-6, and tumor necrosis factor (TNF) α and β. The highest fibrinolytic activity measured by fibrin autography was observed in the conditioned medium of T98G cells treated by IL-1α and TNFα. IL-4 and IL-6 produced a slight increase in fibrinolytic activity, while IL-2 and IL-3 had little effect. Dexamethasone significantly decreased the fibrinolytic activity. Zymographic analysis, ELISA, and Northern blot analysis showed that the increased fibrinolytic activity induced by IL-1 and TNF was caused by increased urokinase-type plasminogen activator (uPA) secretion, and that decreased activity induced by dexamethasone was caused by a decrease in uPA and an increase in type-1 plasminogen activator inhibitor (PAI-1) secretion. These findings suggest that inflammatory mediators are involved in the regulation of brain tumor invasiveness and neovascularization.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 303-307"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80011-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71863697","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":"Pharmacokinetics of the novel plasminogen activator Desmodus rotundus plasminogen activator in animals and extrapolation to man","authors":"M. Hildebrand,&nbsp;A.S. Bhargava,&nbsp;P. Bringmann,&nbsp;A. Schütt,&nbsp;P. Verhallen","doi":"10.1016/S0268-9499(96)80007-5","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80007-5","url":null,"abstract":"<div><p>The novel plasminogen activator <em>Desmodus rotundus</em> plasminogen activator (DSPA), which exhibits high fibrin specificity and thus an interesting pharmacological profile, was characterized pharmacokinetically in rats and cynomolgus monkeys after i.v. bolus administration of ¹²⁵I-labelled protein. Furthermore, several toxicokinetic studies with single or repeated administration of unlabelled DSPA were monitored by ELISA and fibrin clot lysis assay (FCLA) to measure antigen and activity levels. The dose range used in both species was 1 to 30 mg/kg. Data were used to describe the pharmacokinetic profile of DSPA in animals. In rats and monkeys DSPA was characterized by long terminal half-lives of 1–2h and 5–8h with bi- or triphasically declining plasma levels. The terminal phase represented a partial area under the curve (AUC) of 42%–57% in monkeys. Total clearance accounted for 6–11 ml/min/kg and approximately 2 ml/min/kg in rats and monkeys, respectively. The volume of distribution in the central compartment was 0.5–0.1 l/kg in both species. Pharmacokinetics were linear and no sex-specific differences were observed. In both species plasma antigen and activity levels, and thus its pharmacokinetics, showed a linear correlation with a slope close to 1 over the dose range of 1–30 mg/kg. The use of ¹²⁵I-labelled protein only provided limited additional information for the early post-dose phase due to rapid iodine exchange. In terms of distribution in rats, radiolabel indicative for DSPA (i.e. until 30 min post application) was found in the highly perfused organs and tissues. By means of allometric extrapolation a total clearance of approximately 1 ml/min/kg was predicted for humans. DSPA displayed an advantageous pharmacokinetic and pharmacodynamic profile, especially due to its low total clearance, its long terminal half-life, and the complete fibrinolytic activity of antigen present in the plasma, as compared to other established protein fibrinolytics (e.g. t-PA). Animal data encourage the envisaged therapeutic dosage scheme with an i.v. bolus in humans.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 269-276"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80007-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71863700","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":"Contribution of cytokines to hyperfibrinolysis during orthotopic liver transplantation and effect of aprotinin","authors":"J.A. Páramo ,&nbsp;J. A-Cienfuegos ,&nbsp;R. Montes ,&nbsp;J. Hermida ,&nbsp;F. Pardo ,&nbsp;C. Panizo ,&nbsp;E. Rocha","doi":"10.1016/S0268-9499(96)80014-2","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80014-2","url":null,"abstract":"<div><p>A release of inflammatory mediators seems to take place during orthotopic liver transplantation (OLT), which may contribute to the hemostatic abnormalities observed in the reperfusion phase. We investigated 36 patients who underwent their first OLT. The first 10 patients received conventional supportive therapy and the remainder were treated with 400.000 KIH/h of aprotinin, from the beginning of surgery until skin closure. Blood samples were taken before surgery, during the preanhepatic, anhepatic, and reperfusion phases, and daily until the 5th postoperative day to determine tumor necrosis factor (TNF-α), interleukin 6 (IL-6), plasmin-antiplasmin (PAP) complexes, and fibrin degradation products (FbDP). Levels of both cytokines remained unchanged during the preanhepatic phase and increased significantly with the revascularization of the graft liver (<em>P</em> &lt; 0.001) to normalize on postoperative day 3. A hyperfibrinolytic state, as assessed by increased PAP and FbDP, was also observed, starting during the anhepatic phase and reaching maximum expression after reperfusion (<em>P</em> &lt; 0.001). The plasma levels of TNF, IL-6, and FbDP followed a similar pattern along surgery with maximum values during reperfusion. This suggested that cytokines may partially contribute to hyperfibrinolysis during OLT. Aprotinin treatment reduced PAP and FbDP generation (<em>P</em> &lt; 0.01) without influencing the cytokine levels.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 325-329"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80014-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71824416","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":"Differentiation of the roles of the apolipoprotein(a) and LDL moiety in the binding of lipoprotein(a) to limited plasmin digested des AA fibrin","authors":"J. Prins,&nbsp;F.R. Leus,&nbsp;B.N. Bouma,&nbsp;H.J.M. van Rijn","doi":"10.1016/S0268-9499(96)80013-0","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80013-0","url":null,"abstract":"<div><p>Elevated plasma levels of lipoprotein (a) (Lp(a)) in humans represent a major inherited risk factor for atherosclerosis. Lp(a) consists of a LDL-like particle with an additional glycoprotein, apolipoprotein(a) (apo(a)), linked to apolipoprotein B100. The apo(a) moiety is highly homologous to plasminogen as it contains multiple repeats resembling plasminogen kringle IV, a lysine and fibrin binding domain. In the present study, the individual contribution of the two constituents of Lp(a), namely LDL and apo(a), in the binding of Lp(a) to limited plasmin digested des AA fibrin (Desafib-X) is examined.</p><p>Lp(a) was isolated by sequential ultracentrifugation followed by gel filtration chromatography. Lysine binding (Lp(a)lys⁺) and non-lysine binding (Lp(a)lys⁻) Lp(a) were obtained by affinity chromatography using lysine-Sepharose. Lp(a)-free LDL was isolated by ultracentrifugation followed by Lp(a)-free LDL was isolated by ultracentrifugation followed by chromatofocusing. ¹²⁵I-labelled Lp(a), LDL, Lp(a)lys⁻, and Lp(a)lys⁺ preparations were incubated with Desafib-X coated wells in the presence or absence of ɛ-aminocaproic acid (ɛACA, a lysine-analogue) and/or autologous LDL.</p><p>Total Lp(a) contained 86±8% Lp(a)lys⁺. The mean apparent dissociation constant (Kd in nM) for Lp(a), LDL, Lp(a)lys⁻, and Lp(a)lys⁺ binding to Desafib-X was 48±11, 28±4, 7±4, and 43±23, respectively. The binding of Lp(a) and Lp(a)lys⁺ to Desafib-X could be inhibited to a similar degree by 0.2m ɛACA (for 31±14% and 37±15% respectively), indicating lysine specific binding of these preparations. The binding of Lp(a)lys⁻ and LDL could not be inhibited by ɛACA. A ten times molar excess of LDL could inhibit the binding of Lp(a), Lp(a)lys⁻, and Lp(a)lys⁺ to Desafib-X by 60 to 80%. For Lp(a) and Lp(a)lys⁺, an additional binding-inhibition can be observed when adding 0.2M ɛACA.</p><p>In conclusion, the overall findings indicate that the binding of Lp(a) to fibrin(-ogen) is more complex than previously thought and imposes an influence of the LDL moiety and LDL, additional to the apo(a) moiety, in the binding of Lp(a) to lysine-containing proteins like Desafib-X.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 317-324"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80013-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71778732","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":"Fibrinolysis in insulin-dependent diabetic patients with and without nephropathy","authors":"B. Myrup ,&nbsp;P. Rossing ,&nbsp;T. Jensen ,&nbsp;J. Gram ,&nbsp;C. Kluft ,&nbsp;J. Jespersen","doi":"10.1016/S0268-9499(96)80015-4","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80015-4","url":null,"abstract":"<div><p><strong>Objective:</strong> To investigate possible contributions from fibrinolytic disturbances to susceptibility for cardiovascular complications in insulin-dependent diabetic patients with nephropathy.</p><p><strong>Design:</strong> Cross-sectional study.</p><p><strong>Setting:</strong> Outpatient diabetic clinic in a tertiary hospital.</p><p><strong>Subjects:</strong> Insulin-dependent diabetic patients without diabetic nephropathy (normoalbuminuria, <em>n</em> = 17), patients with incipient diabetic nephropathy (<em>n</em> = 19), and patients with diabetic nephropathy (<em>n</em> = 13). Non-diabetic subjects served as a control group (<em>n</em> = 14).</p><p><strong>Results:</strong> Tissue-type plasminogen activator antigen and plasminogen activator inhibitor type 1 were lower in diabetic patients, irrespective of the level of albuminuria. Tissue-type plasminogen activator activity measured in acidified plasma by bioimmunoassay was increased in normoalbuminuria, while the level in diabetic nephropathy was not different from a non-diabetic control level, and was significantly lower than in the normoalbuminuric group. D-Dimer and soluble fibrin were elevated in the pooled group of diabetic patients and were not influenced by presence of nephropathy. The level of plasmin-α₂-antiplasmin complexes was elevated to the same extent in each group of insulin-dependent diabetic patients.</p><p><strong>Conclusion:</strong> The data suggest increased fibrinogen turnover in insulin-dependent diabetes mellitus, irrespective of the presence of nephropathy. In normoalbuminuric patients, an increase in plasminogen activation could be explained by increased activity of tissue plasminogen activator, while other explanations, e.g. fibrin accumulation, probably connected to developing atherogenesis, could be hypothesized in patients with nephropathy.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 331-335"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80015-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71824418","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":"Fibroblast growth factor 2 and the protease activity of tumor cells isolated from BK virus/tat transgenic mice","authors":"J.A.M. Maier ,&nbsp;M. Mariotti ,&nbsp;L. Meneghini ,&nbsp;U. Cavallaro ,&nbsp;Z. Wu ,&nbsp;G. Massazza ,&nbsp;D. Campioni ,&nbsp;A. Corallini ,&nbsp;G. Barbanti-Brodano ,&nbsp;M.R. Soria","doi":"10.1016/S0268-9499(96)80012-9","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80012-9","url":null,"abstract":"<div><p>In BK virus (BKV)/<em>tat</em> transgenic mice, the relatively low incidence and long latency period of tumors indicate that the BKV/<em>tat</em> transgene is not sufficient for the expression of a complete oncogenic phenotype. Since angiogenesis and the production of proteases are critical for tumor growth, we evaluated the expression of two potent angiogenic molecules, fibroblast growth factor type 2 (FGF-2), and hepatocyte growth factor (HGF), and of the fibrinolytic system in cell lines isolated from tumors of different histotypes developed by BKV/<em>tat</em> transgenic mice. Here we show that the overexpression of HGF is a unique feature of spindle cells derived from murine Kaposi's sarcoma-like lesions, whereas FGF-2 is detectable in all the cell lines tested. Interestingly, FGF-2 is secreted only by adenocarcinoma-derived T53 cells that show a fully transformed phenotype in vitro. In addition, T53 cells synthesize larger amounts of urokinase-type plasminogen activator (uPA) than the other cell lines studied. This is due to the secretion of FGF-2 and not to the presence of extracellular Tat. We conclude that the high levels of expression of uPA and its receptor, and the very low levels of plasminogen activator inhibitor type 1, may contribute to the tumorigenic phenotype of T53 cells.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 309-315"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80012-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71863698","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":"Production of plasminogen activator inhibitor type-2 in human peripheral blood monocytes upregulated in vitro by the quinoline-3-carboxamide, Linomide","authors":"A. Billström ,&nbsp;B. Kinnby ,&nbsp;I. Lecander ,&nbsp;B. Åstedt","doi":"10.1016/S0268-9499(96)80008-7","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80008-7","url":null,"abstract":"<div><p>Cumulative evidence suggests plasminogen activator inhibitor type-2 (PAI-2) has a tumor suppressive effect owing to its inhibition of urokinase-type plasminogen activator (u-PA) activity. One strategy for anti-tumor treatment might be to stimulate the endogenous production of PAI-2 by monocytes/macrophages. In the present study, human peripheral blood mononuclear cells (PBMC) were incubated with Linomide, a quinoline-3-carboxamide previously shown to exert anti-tumor effects in several animal models. We found Linomide to increase the antigen concentration and enhance the mRNA levels of PAI-2 in a dose-dependent way. In situ hybridization, performed to localize PAI-2 mRNA in PBMC, showed PAI-2 to be exclusively expressed in the monocyte population in which Linomide treatment induced enhanced mRNA expression. Stimulation of endogenous PAI-2 production might be a new approach in tumor therapy.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 277-283"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80008-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71863699","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":"Thrombolysis with tissue plasminogen activator enhances serum lipoprotein(a) levels compared to streptokinase and conservative treatment in patients with acute myocardial infarction","authors":"M. Paassilta ,&nbsp;K. Kervinen ,&nbsp;K.J. Peuhkurinen ,&nbsp;Y.A. Kesäniemi","doi":"10.1016/S0268-9499(96)80006-3","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80006-3","url":null,"abstract":"<div><p>Lp(a) may interfere with thrombosis and thrombolysis. We followed Lp(a) levels in 20 patients with acute myocardial infarction randomized to receive streptokinase (SK, <em>n</em>=10) or tissue-plasminogen activator (t-PA, <em>n</em>=10). The results were compared to those obtained with five patients treated conservatively. Baseline characteristics were equal in the study groups. Lp(a) levels increased significantly, (22.1%) during t-PA infusion (<em>P</em>&lt;0.005 t-PA vs SK, <em>P</em>&lt;0.005 t-PA vs conservative treatment), but they remained unchanged during SK infusion and conservative treatment. In all three groups, a more prominent increase in serum Lp(a) levels, (51.8%, 24.4%, and 36.8% for the t-PA, SK, and conservative treatment groups, respectively), was observed 3 days after the admission to the hospital, probably reflecting an acute phase reaction. Although the size of the study is relatively small, the suggested linkage between Lp(a) and thrombolytic treatment with t-PA may be of interest, and the mechanisms behind it need to be elucidated. The alterations in Lp(a) levels may be involved in the complex interactions between thrombolytic agents, thrombus, clotting cascade, and endothelium affecting thrombolysis and reocclusion.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 263-268"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80006-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71863704","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":"Receptor-mediated effect of thrombin on plasminogen activator inhibitor-1 synthesis in rat osteoblast-like cells","authors":"E.H. Allan,&nbsp;T.J. Martin","doi":"10.1016/S0268-9499(96)80009-9","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80009-9","url":null,"abstract":"<div><p>The effect of thrombin on components of the plasminogen activator (PA)/plasmin pathway in osteoblast-like cells has been investigated. Thrombin was found to increase PA inhibitor-1 (PAI-1) mRNA and protein in a time- and dose-dependent manner. Tissue-type plasminogen activator (t-PA) activity was inhibited in a time- and dose-dependent manner but there was no alteration of t-PA steady-state mRNA levels. Therefore it is likely that the inhibition of t-PA activity was due entirely to the inhibition of t-PA by PAI-1. Thrombin induced a small but consistent transient increase in both urokinase-type plasminogen activator (u-PA) and u-PA receptor mRNA levels but no u-PA activity was detectable by the amidolytic assay used here. The thrombin and u-PAI inhibitor protease nexin (PN-1), present in high levels constitutively in these cells, was found to be unaltered by thrombin treatment. The effects of thrombin on PAI-1 mRNA and protein and t-PA activity appear to be mediated by the thrombin receptor since the thrombin receptor activating peptide, SFLLRN (single letter code for amino acids), was able to mimic the effects of thrombin. Thrombin has been reported to induce prostaglandin synthesis in rat osteoblasts, and several actions of thrombin on osteoblasts have been reported to be partially dependent on prostaglandin synthesis. However, the effects of both thrombin and SFLLRN on PAI-1 protein were found to be independent of prostaglandin synthesis.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 5","pages":"Pages 285-293"},"PeriodicalIF":0.0,"publicationDate":"1996-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80009-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71864316","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}