Fibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion
Fibrin polymerization is a necessary part of hemostasis but clots can obstruct blood vessels and cause heart attacks and strokes. The polymerization reactions are specific and controlled, involving strong knob-into-hole interactions to convert soluble fibrinogen into insoluble fibrin. It has long be...
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description | Fibrin polymerization is a necessary part of hemostasis but clots can obstruct blood vessels and cause heart attacks and strokes. The polymerization reactions are specific and controlled, involving strong knob-into-hole interactions to convert soluble fibrinogen into insoluble fibrin. It has long been assumed that clots and thrombi are stable structures until proteolytic digestion. On the contrary, using the technique of fluorescence recovery after photobleaching, we demonstrate here that there is turnover of fibrin in an uncrosslinked clot. A peptide representing the knobs involved in fibrin polymerization can compete for the holes and dissolve a preformed fibrin clot, or increase the fraction of soluble oligomers, with striking rearrangements in clot structure. These results imply that
in vivo
clots or thrombi are more dynamic structures than previously believed that may be remodeled as a result of local environmental conditions, may account for some embolization and suggest a target for therapeutic intervention. |
doi_str_mv | 10.1038/srep00879 |
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in vivo
clots or thrombi are more dynamic structures than previously believed that may be remodeled as a result of local environmental conditions, may account for some embolization and suggest a target for therapeutic intervention.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep00879</identifier><identifier>PMID: 23170200</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/57/2272/2276 ; 631/80 ; 639/301/54/1754 ; 639/705/1041 ; Blood Coagulation - physiology ; Blood vessels ; Digestion ; Embolization ; Environmental conditions ; Fibrin ; Fibrin - metabolism ; Fibrinogen ; Fibrinogen - metabolism ; Fluorescence recovery after photobleaching ; Hemostasis ; Humanities and Social Sciences ; Humans ; multidisciplinary ; Photobleaching ; Polymerization ; Polymers ; Polymers - metabolism ; Proteolysis ; Science ; Stroke ; Thrombin - metabolism</subject><ispartof>Scientific reports, 2012-11, Vol.2 (1), p.879-879, Article 879</ispartof><rights>The Author(s) 2012</rights><rights>Copyright Nature Publishing Group Nov 2012</rights><rights>Copyright © 2012, Macmillan Publishers Limited. All rights reserved 2012 Macmillan Publishers Limited. All rights reserved</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-c9d2c655be15b0c7ab11d5de4fae611e775371a903c8584b88f910bf4359254a3</citedby><cites>FETCH-LOGICAL-c438t-c9d2c655be15b0c7ab11d5de4fae611e775371a903c8584b88f910bf4359254a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501649/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501649/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51554,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23170200$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chernysh, Irina N.</creatorcontrib><creatorcontrib>Nagaswami, Chandrasekaran</creatorcontrib><creatorcontrib>Purohit, Prashant K.</creatorcontrib><creatorcontrib>Weisel, John W.</creatorcontrib><title>Fibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Fibrin polymerization is a necessary part of hemostasis but clots can obstruct blood vessels and cause heart attacks and strokes. The polymerization reactions are specific and controlled, involving strong knob-into-hole interactions to convert soluble fibrinogen into insoluble fibrin. It has long been assumed that clots and thrombi are stable structures until proteolytic digestion. On the contrary, using the technique of fluorescence recovery after photobleaching, we demonstrate here that there is turnover of fibrin in an uncrosslinked clot. A peptide representing the knobs involved in fibrin polymerization can compete for the holes and dissolve a preformed fibrin clot, or increase the fraction of soluble oligomers, with striking rearrangements in clot structure. These results imply that
in vivo
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Nagaswami, Chandrasekaran ; Purohit, Prashant K. ; Weisel, John W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-c9d2c655be15b0c7ab11d5de4fae611e775371a903c8584b88f910bf4359254a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>631/57/2272/2276</topic><topic>631/80</topic><topic>639/301/54/1754</topic><topic>639/705/1041</topic><topic>Blood Coagulation - physiology</topic><topic>Blood vessels</topic><topic>Digestion</topic><topic>Embolization</topic><topic>Environmental conditions</topic><topic>Fibrin</topic><topic>Fibrin - metabolism</topic><topic>Fibrinogen</topic><topic>Fibrinogen - metabolism</topic><topic>Fluorescence recovery after photobleaching</topic><topic>Hemostasis</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>multidisciplinary</topic><topic>Photobleaching</topic><topic>Polymerization</topic><topic>Polymers</topic><topic>Polymers - metabolism</topic><topic>Proteolysis</topic><topic>Science</topic><topic>Stroke</topic><topic>Thrombin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chernysh, Irina N.</creatorcontrib><creatorcontrib>Nagaswami, Chandrasekaran</creatorcontrib><creatorcontrib>Purohit, Prashant K.</creatorcontrib><creatorcontrib>Weisel, John W.</creatorcontrib><collection>Springer Nature OA Free Journals</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 Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chernysh, Irina N.</au><au>Nagaswami, Chandrasekaran</au><au>Purohit, Prashant K.</au><au>Weisel, John W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2012-11-20</date><risdate>2012</risdate><volume>2</volume><issue>1</issue><spage>879</spage><epage>879</epage><pages>879-879</pages><artnum>879</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Fibrin polymerization is a necessary part of hemostasis but clots can obstruct blood vessels and cause heart attacks and strokes. The polymerization reactions are specific and controlled, involving strong knob-into-hole interactions to convert soluble fibrinogen into insoluble fibrin. It has long been assumed that clots and thrombi are stable structures until proteolytic digestion. On the contrary, using the technique of fluorescence recovery after photobleaching, we demonstrate here that there is turnover of fibrin in an uncrosslinked clot. A peptide representing the knobs involved in fibrin polymerization can compete for the holes and dissolve a preformed fibrin clot, or increase the fraction of soluble oligomers, with striking rearrangements in clot structure. These results imply that
in vivo
clots or thrombi are more dynamic structures than previously believed that may be remodeled as a result of local environmental conditions, may account for some embolization and suggest a target for therapeutic intervention.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23170200</pmid><doi>10.1038/srep00879</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 631/57/2272/2276 631/80 639/301/54/1754 639/705/1041 Blood Coagulation - physiology Blood vessels Digestion Embolization Environmental conditions Fibrin Fibrin - metabolism Fibrinogen Fibrinogen - metabolism Fluorescence recovery after photobleaching Hemostasis Humanities and Social Sciences Humans multidisciplinary Photobleaching Polymerization Polymers Polymers - metabolism Proteolysis Science Stroke Thrombin - metabolism |
title | Fibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion |
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