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
Hauptverfasser: Marcinkiewicz, Marek, Gordon, Phillip V
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creator Marcinkiewicz, Marek
Gordon, Phillip V
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.
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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 &amp; 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 &amp; 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 &amp; 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 &amp; 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 &amp; 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 &amp; 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 &amp; 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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