Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia
OBJECTIVE—Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. METHODS AND RESULTS—To determine th...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2004-03, Vol.24 (3), p.483-488 |
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| container_title | Arteriosclerosis, thrombosis, and vascular biology |
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| creator | Renckens, Rosemarijn Weijer, Sebastiaan de Vos, Alex F Pater, Jennie M Meijers, Joost C Hack, C Erik Levi, Marcel van der Poll, Tom |
| description | OBJECTIVE—Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems.
METHODS AND RESULTS—To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n = 8), a plasmin activation inhibitor, or placebo (n=8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-α2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both P |
| doi_str_mv | 10.1161/01.ATV.0000118280.95422.48 |
| format | Article |
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METHODS AND RESULTS—To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n = 8), a plasmin activation inhibitor, or placebo (n=8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-α2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both P <0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-α1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release.
CONCLUSION—These data argue against a role of early plasmin generation in the subsequent activation of other inflammatory pathways during human endotoxemia.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.ATV.0000118280.95422.48</identifier><identifier>PMID: 14739127</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Adult ; Antithrombin III - analysis ; Atherosclerosis (general aspects, experimental research) ; Binding, Competitive ; Biological and medical sciences ; Biomarkers ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cytokines - blood ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Endotoxemia - blood ; Fibrin Fibrinogen Degradation Products - analysis ; Fibrinolysin - biosynthesis ; Fibrinolysis - drug effects ; Humans ; Lipopolysaccharides - toxicity ; Male ; Medical sciences ; Peptide Fragments - analysis ; Peptide Hydrolases - analysis ; Plasminogen - metabolism ; Prothrombin - analysis ; Tranexamic Acid - pharmacology</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2004-03, Vol.24 (3), p.483-488</ispartof><rights>2004 American Heart Association, Inc.</rights><rights>2004 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Mar 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5597-49e2a46e44e93d701df8767525ea1f955861ff27b1a9d00d4a151e659cc5e5513</citedby><cites>FETCH-LOGICAL-c5597-49e2a46e44e93d701df8767525ea1f955861ff27b1a9d00d4a151e659cc5e5513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15590863$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14739127$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Renckens, Rosemarijn</creatorcontrib><creatorcontrib>Weijer, Sebastiaan</creatorcontrib><creatorcontrib>de Vos, Alex F</creatorcontrib><creatorcontrib>Pater, Jennie M</creatorcontrib><creatorcontrib>Meijers, Joost C</creatorcontrib><creatorcontrib>Hack, C Erik</creatorcontrib><creatorcontrib>Levi, Marcel</creatorcontrib><creatorcontrib>van der Poll, Tom</creatorcontrib><title>Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems.
METHODS AND RESULTS—To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n = 8), a plasmin activation inhibitor, or placebo (n=8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-α2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both P <0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-α1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release.
CONCLUSION—These data argue against a role of early plasmin generation in the subsequent activation of other inflammatory pathways during human endotoxemia.</description><subject>Adult</subject><subject>Antithrombin III - analysis</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cytokines - blood</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Endotoxemia - blood</subject><subject>Fibrin Fibrinogen Degradation Products - analysis</subject><subject>Fibrinolysin - biosynthesis</subject><subject>Fibrinolysis - drug effects</subject><subject>Humans</subject><subject>Lipopolysaccharides - toxicity</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Peptide Fragments - analysis</subject><subject>Peptide Hydrolases - analysis</subject><subject>Plasminogen - metabolism</subject><subject>Prothrombin - analysis</subject><subject>Tranexamic Acid - pharmacology</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkF1v2yAUhtG0qV_rX5hQpV3a5WDAZndR27WRqq0X2W4RsfFCZ0MHeKn_fUkTKdxwQM85LzwIXQEpAQRcEygXq98lyQugoQ0pJWeUlqz5gM6AU1YwUYmPuSa1LLhg9BSdx_ic-YyRE3QKrK4k0PoMxaXb2LVN1jvse_w06Dhahxdtsv9tmvF6xqugnXnVo23zte3wrTcR__AJL10_TMa15r3S46iTDzN-0mmz1XPEt1Ow7g9-mEbt8J3rfPKvZrT6M_rU6yGay8N-gX59v1vdPBSPP--XN4vHouVc1gWThmomDGNGVl1NoOubWtSccqOhl5w3Avqe1mvQsiOkYxo4GMFl23LDOVQX6Go_9yX4f5OJST37KbgcqWg20Qghmwx920Nt8DEG06uXYEcdZgVE7XQrAirrVkfd6l23YrvmL4eEaT2a7th68JuBrwdAx1YPfVbZ2njk8kdJI6rMsT239UMyIf4dpq0JamP0kDa7aFYJwguaC1LlY7F7TF29Adn0mB4</recordid><startdate>200403</startdate><enddate>200403</enddate><creator>Renckens, Rosemarijn</creator><creator>Weijer, Sebastiaan</creator><creator>de Vos, Alex F</creator><creator>Pater, Jennie M</creator><creator>Meijers, Joost C</creator><creator>Hack, C Erik</creator><creator>Levi, Marcel</creator><creator>van der Poll, Tom</creator><general>American Heart Association, Inc</general><general>Lippincott</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope></search><sort><creationdate>200403</creationdate><title>Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia</title><author>Renckens, Rosemarijn ; Weijer, Sebastiaan ; de Vos, Alex F ; Pater, Jennie M ; Meijers, Joost C ; Hack, C Erik ; Levi, Marcel ; van der Poll, Tom</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5597-49e2a46e44e93d701df8767525ea1f955861ff27b1a9d00d4a151e659cc5e5513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Antithrombin III - analysis</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cytokines - blood</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Endotoxemia - blood</topic><topic>Fibrin Fibrinogen Degradation Products - analysis</topic><topic>Fibrinolysin - biosynthesis</topic><topic>Fibrinolysis - drug effects</topic><topic>Humans</topic><topic>Lipopolysaccharides - toxicity</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Peptide Fragments - analysis</topic><topic>Peptide Hydrolases - analysis</topic><topic>Plasminogen - metabolism</topic><topic>Prothrombin - analysis</topic><topic>Tranexamic Acid - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Renckens, Rosemarijn</creatorcontrib><creatorcontrib>Weijer, Sebastiaan</creatorcontrib><creatorcontrib>de Vos, Alex F</creatorcontrib><creatorcontrib>Pater, Jennie M</creatorcontrib><creatorcontrib>Meijers, Joost C</creatorcontrib><creatorcontrib>Hack, C Erik</creatorcontrib><creatorcontrib>Levi, Marcel</creatorcontrib><creatorcontrib>van der Poll, Tom</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Renckens, Rosemarijn</au><au>Weijer, Sebastiaan</au><au>de Vos, Alex F</au><au>Pater, Jennie M</au><au>Meijers, Joost C</au><au>Hack, C Erik</au><au>Levi, Marcel</au><au>van der Poll, Tom</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2004-03</date><risdate>2004</risdate><volume>24</volume><issue>3</issue><spage>483</spage><epage>488</epage><pages>483-488</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>OBJECTIVE—Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems.
METHODS AND RESULTS—To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n = 8), a plasmin activation inhibitor, or placebo (n=8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-α2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both P <0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-α1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release.
CONCLUSION—These data argue against a role of early plasmin generation in the subsequent activation of other inflammatory pathways during human endotoxemia.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>14739127</pmid><doi>10.1161/01.ATV.0000118280.95422.48</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2004-03, Vol.24 (3), p.483-488 |
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| subjects | Adult Antithrombin III - analysis Atherosclerosis (general aspects, experimental research) Binding, Competitive Biological and medical sciences Biomarkers Blood and lymphatic vessels Cardiology. Vascular system Cytokines - blood Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Endotoxemia - blood Fibrin Fibrinogen Degradation Products - analysis Fibrinolysin - biosynthesis Fibrinolysis - drug effects Humans Lipopolysaccharides - toxicity Male Medical sciences Peptide Fragments - analysis Peptide Hydrolases - analysis Plasminogen - metabolism Prothrombin - analysis Tranexamic Acid - pharmacology |
| title | Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia |
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