A role for plasmin in platelet aggregation: Differential regulation of IGF release from IGF–IGFBP complexes?
Abstract Objectives To determine if plasmin differentially augments platelet aggregation through variable efficiencies of IGF–IGFBP complex cleavage. Methods We utilized ADP-triggered platelet aggregation assays to test the effects of IGF-I versus IGF-II in complex with IGFBP-2 or IGFBP-3 upon the e...
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Veröffentlicht in: | Growth hormone & IGF research 2008-08, Vol.18 (4), p.325-334 |
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description | Abstract Objectives To determine if plasmin differentially augments platelet aggregation through variable efficiencies of IGF–IGFBP complex cleavage. Methods We utilized ADP-triggered platelet aggregation assays to test the effects of IGF-I versus IGF-II in complex with IGFBP-2 or IGFBP-3 upon the efficiency of plasmin (a known IGFBP protease) as a pro-aggregatory stimulus. In vitro proteolysis assays were performed as controls. Results We found that IGF-I complexes augmented platelet-mediated aggregation whereas IGF-II either had no effect (IGFBP-2) or inhibited platelet-mediated aggregation (IGFBP-3). In vitro proteolysis assays of IGFBP-2 and IGFBP-3 using plasmin revealed that three of the four aggregation findings were explained by the disparate efficiencies of IGFBP proteolysis associated with each IGF. Only IGF-II–IGFBP-2 complex resulted in a finding that could not be explained by the concept of differential regulation of plasmin’s proteolysis efficiency by the two IGF ligands. Conclusions Our findings demonstrate that the plasmin can differentially modulate platelet aggregation in response to intrinsic heterogeneities within the IGF axis. |
doi_str_mv | 10.1016/j.ghir.2008.01.004 |
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Methods We utilized ADP-triggered platelet aggregation assays to test the effects of IGF-I versus IGF-II in complex with IGFBP-2 or IGFBP-3 upon the efficiency of plasmin (a known IGFBP protease) as a pro-aggregatory stimulus. In vitro proteolysis assays were performed as controls. Results We found that IGF-I complexes augmented platelet-mediated aggregation whereas IGF-II either had no effect (IGFBP-2) or inhibited platelet-mediated aggregation (IGFBP-3). In vitro proteolysis assays of IGFBP-2 and IGFBP-3 using plasmin revealed that three of the four aggregation findings were explained by the disparate efficiencies of IGFBP proteolysis associated with each IGF. Only IGF-II–IGFBP-2 complex resulted in a finding that could not be explained by the concept of differential regulation of plasmin’s proteolysis efficiency by the two IGF ligands. Conclusions Our findings demonstrate that the plasmin can differentially modulate platelet aggregation in response to intrinsic heterogeneities within the IGF axis.</description><identifier>ISSN: 1096-6374</identifier><identifier>EISSN: 1532-2238</identifier><identifier>DOI: 10.1016/j.ghir.2008.01.004</identifier><identifier>PMID: 18328759</identifier><language>eng</language><publisher>Scotland: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Aggregation ; Blood Platelets - drug effects ; Blood Platelets - metabolism ; Endocrinology & Metabolism ; Fibrinolysin - metabolism ; Fibrinolysin - physiology ; Humans ; IGF-binding protein ; Indomethacin - pharmacology ; Insulin-like growth factor ; Insulin-Like Growth Factor Binding Proteins - metabolism ; Models, Biological ; Multiprotein Complexes - metabolism ; Plasmin ; Platelet aggregation ; Platelet Aggregation - drug effects ; Platelet Aggregation - physiology ; Protein Binding ; Protein Processing, Post-Translational ; Somatomedins - metabolism ; Somatomedins - secretion</subject><ispartof>Growth hormone & IGF research, 2008-08, Vol.18 (4), p.325-334</ispartof><rights>Elsevier Ltd</rights><rights>2008 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-fad87f128aa0e9eae80ab6f0b633e12fa360e6c0d8703b3c4089989aac2df19d3</citedby><cites>FETCH-LOGICAL-c409t-fad87f128aa0e9eae80ab6f0b633e12fa360e6c0d8703b3c4089989aac2df19d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1096637408000051$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18328759$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marcinkiewicz, Marek</creatorcontrib><creatorcontrib>Gordon, Phillip V</creatorcontrib><title>A role for plasmin in platelet aggregation: Differential regulation of IGF release from IGF–IGFBP complexes?</title><title>Growth hormone & IGF research</title><addtitle>Growth Horm IGF Res</addtitle><description>Abstract Objectives To determine if plasmin differentially augments platelet aggregation through variable efficiencies of IGF–IGFBP complex cleavage. Methods We utilized ADP-triggered platelet aggregation assays to test the effects of IGF-I versus IGF-II in complex with IGFBP-2 or IGFBP-3 upon the efficiency of plasmin (a known IGFBP protease) as a pro-aggregatory stimulus. In vitro proteolysis assays were performed as controls. Results We found that IGF-I complexes augmented platelet-mediated aggregation whereas IGF-II either had no effect (IGFBP-2) or inhibited platelet-mediated aggregation (IGFBP-3). In vitro proteolysis assays of IGFBP-2 and IGFBP-3 using plasmin revealed that three of the four aggregation findings were explained by the disparate efficiencies of IGFBP proteolysis associated with each IGF. Only IGF-II–IGFBP-2 complex resulted in a finding that could not be explained by the concept of differential regulation of plasmin’s proteolysis efficiency by the two IGF ligands. Conclusions Our findings demonstrate that the plasmin can differentially modulate platelet aggregation in response to intrinsic heterogeneities within the IGF axis.</description><subject>Advanced Basic Science</subject><subject>Aggregation</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - metabolism</subject><subject>Endocrinology & Metabolism</subject><subject>Fibrinolysin - metabolism</subject><subject>Fibrinolysin - physiology</subject><subject>Humans</subject><subject>IGF-binding protein</subject><subject>Indomethacin - pharmacology</subject><subject>Insulin-like growth factor</subject><subject>Insulin-Like Growth Factor Binding Proteins - metabolism</subject><subject>Models, Biological</subject><subject>Multiprotein Complexes - metabolism</subject><subject>Plasmin</subject><subject>Platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation - physiology</subject><subject>Protein Binding</subject><subject>Protein Processing, Post-Translational</subject><subject>Somatomedins - metabolism</subject><subject>Somatomedins - secretion</subject><issn>1096-6374</issn><issn>1532-2238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kd9qFDEUxoMo9o--gBeSK-9mPEl2Z5Milv6xtVBQsL0O2czJmm1msk1mxN75Dn1Dn8SMuyD0QgjJ4eT7Pji_Q8gbBjUD1rxf16vvPtUcQNbAaoDZM7LP5oJXnAv5vNSgmqoRi9keOch5DQBKyNlLssek4HIxV_ukP6EpBqQuJroJJne-p-WUcsCAAzWrVcKVGXzsj-i5dw4T9oM3gZb2GP5-0Ojo1eVF6QQ0uWSl2E2N378ey336ldrYbQL-xHz8irxwJmR8vXsPye3Fp5uzz9X1l8urs5Prys5ADZUzrVw4xqUxgAoNSjDLxsGyEQIZd0Y0gI2FogKxFMUklZLKGMtbx1QrDsm7be4mxfsR86A7ny2GYHqMY9YL1hQGUhQh3wptijkndHqTfGfSg2agJ8p6rSfKeqKsgelCuZje7tLHZYftP8sOaxF82AqwzPjDY9LZeuwttj6hHXQb_f_zPz6x2-B7b024wwfM6zimvtDTTGeuQX-b9jytGWRZMcyZ-AOJ3qQ9</recordid><startdate>20080801</startdate><enddate>20080801</enddate><creator>Marcinkiewicz, Marek</creator><creator>Gordon, Phillip V</creator><general>Elsevier Ltd</general><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>7X8</scope></search><sort><creationdate>20080801</creationdate><title>A role for plasmin in platelet aggregation: Differential regulation of IGF release from IGF–IGFBP complexes?</title><author>Marcinkiewicz, Marek ; Gordon, Phillip V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-fad87f128aa0e9eae80ab6f0b633e12fa360e6c0d8703b3c4089989aac2df19d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Advanced Basic Science</topic><topic>Aggregation</topic><topic>Blood Platelets - drug effects</topic><topic>Blood Platelets - metabolism</topic><topic>Endocrinology & Metabolism</topic><topic>Fibrinolysin - metabolism</topic><topic>Fibrinolysin - physiology</topic><topic>Humans</topic><topic>IGF-binding protein</topic><topic>Indomethacin - pharmacology</topic><topic>Insulin-like growth factor</topic><topic>Insulin-Like Growth Factor Binding Proteins - metabolism</topic><topic>Models, Biological</topic><topic>Multiprotein Complexes - metabolism</topic><topic>Plasmin</topic><topic>Platelet aggregation</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Aggregation - physiology</topic><topic>Protein Binding</topic><topic>Protein Processing, Post-Translational</topic><topic>Somatomedins - metabolism</topic><topic>Somatomedins - secretion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marcinkiewicz, Marek</creatorcontrib><creatorcontrib>Gordon, Phillip V</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Growth hormone & IGF research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marcinkiewicz, Marek</au><au>Gordon, Phillip V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A role for plasmin in platelet aggregation: Differential regulation of IGF release from IGF–IGFBP complexes?</atitle><jtitle>Growth hormone & IGF research</jtitle><addtitle>Growth Horm IGF Res</addtitle><date>2008-08-01</date><risdate>2008</risdate><volume>18</volume><issue>4</issue><spage>325</spage><epage>334</epage><pages>325-334</pages><issn>1096-6374</issn><eissn>1532-2238</eissn><abstract>Abstract Objectives To determine if plasmin differentially augments platelet aggregation through variable efficiencies of IGF–IGFBP complex cleavage. Methods We utilized ADP-triggered platelet aggregation assays to test the effects of IGF-I versus IGF-II in complex with IGFBP-2 or IGFBP-3 upon the efficiency of plasmin (a known IGFBP protease) as a pro-aggregatory stimulus. In vitro proteolysis assays were performed as controls. Results We found that IGF-I complexes augmented platelet-mediated aggregation whereas IGF-II either had no effect (IGFBP-2) or inhibited platelet-mediated aggregation (IGFBP-3). In vitro proteolysis assays of IGFBP-2 and IGFBP-3 using plasmin revealed that three of the four aggregation findings were explained by the disparate efficiencies of IGFBP proteolysis associated with each IGF. Only IGF-II–IGFBP-2 complex resulted in a finding that could not be explained by the concept of differential regulation of plasmin’s proteolysis efficiency by the two IGF ligands. Conclusions Our findings demonstrate that the plasmin can differentially modulate platelet aggregation in response to intrinsic heterogeneities within the IGF axis.</abstract><cop>Scotland</cop><pub>Elsevier Ltd</pub><pmid>18328759</pmid><doi>10.1016/j.ghir.2008.01.004</doi><tpages>10</tpages></addata></record> |
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subjects | Advanced Basic Science Aggregation Blood Platelets - drug effects Blood Platelets - metabolism Endocrinology & Metabolism Fibrinolysin - metabolism Fibrinolysin - physiology Humans IGF-binding protein Indomethacin - pharmacology Insulin-like growth factor Insulin-Like Growth Factor Binding Proteins - metabolism Models, Biological Multiprotein Complexes - metabolism Plasmin Platelet aggregation Platelet Aggregation - drug effects Platelet Aggregation - physiology Protein Binding Protein Processing, Post-Translational Somatomedins - metabolism Somatomedins - secretion |
title | A role for plasmin in platelet aggregation: Differential regulation of IGF release from IGF–IGFBP complexes? |
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