{"id":2685,"date":"2020-06-22T14:46:53","date_gmt":"2020-06-22T18:46:53","guid":{"rendered":"https:\/\/www.med.unc.edu\/wolberglab\/?p=2685"},"modified":"2020-07-27T17:12:23","modified_gmt":"2020-07-27T21:12:23","slug":"new-publication-in-blood-2","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/wolberglab\/new-publication-in-blood-2\/","title":{"rendered":"New publication in Blood"},"content":{"rendered":"<h4 class=\"wi-article-title article-title-main\"><a href=\"https:\/\/ashpublications.org\/blood\/article\/135\/19\/1704\/452492\/A-high-fat-diet-delays-plasmin-generation-in-a\">A high-fat diet delays plasmin generation in a thrombomodulin-dependent manner in mice<\/a><\/h4>\n<h5 id=\"9609411\" class=\"abstract-title\"><span style=\"color: inherit\">Obesity is a prevalent prothrombotic risk factor marked by enhanced fibrin formation and suppressed fibrinolysis. Fibrin both promotes thrombotic events and drives obesity pathophysiology, but a lack of essential analytical tools has left fibrinolytic mechanisms affected by obesity poorly defined. Using a plasmin-specific fluorogenic substrate, we developed a plasmin generation (PG) assay for mouse plasma that is sensitive to tissue plasminogen activator, \u03b1<\/span><sub style=\"color: inherit\">2<\/sub><span style=\"color: inherit\">-antiplasmin, active plasminogen activator inhibitor (PAI-1), and fibrin formation, but not fibrin crosslinking. Compared with plasmas from mice fed a control diet, plasmas from mice fed a high-fat diet (HFD) showed delayed PG and reduced PG velocity. Concurrent to impaired PG, HFD also enhanced thrombin generation (TG). The collective impact of abnormal TG and PG in HFD-fed mice produced normal fibrin formation kinetics but delayed fibrinolysis. Functional and proteomic analyses determined that delayed PG in HFD-fed mice was not due to altered levels of plasminogen, \u03b1<\/span><sub style=\"color: inherit\">2<\/sub><span style=\"color: inherit\">-antiplasmin, or fibrinogen. Changes in PG were also not explained by elevated PAI-1 because active PAI-1 concentrations required to inhibit the PG assay were 100-fold higher than circulating concentrations in mice. HFD-fed mice had increased circulating thrombomodulin, and inhibiting thrombomodulin or thrombin-activatable fibrinolysis inhibitor (TAFI) normalized PG, revealing a thrombomodulin- and TAFI-dependent antifibrinolytic mechanism. Integrating kinetic parameters to calculate the metric of TG\/PG ratio revealed a quantifiable net shift toward a prothrombotic phenotype in HFD-fed mice. Integrating TG and PG measurements may define a prothrombotic risk factor in diet-induced obesity.<\/span><\/h5>\n","protected":false},"excerpt":{"rendered":"<p>A high-fat diet delays plasmin generation in a thrombomodulin-dependent manner in mice Obesity is a prevalent prothrombotic risk factor marked by enhanced fibrin formation and suppressed fibrinolysis. Fibrin both promotes thrombotic events and drives obesity pathophysiology, but a lack of essential analytical tools has left fibrinolytic mechanisms affected by obesity poorly defined. Using a plasmin-specific &hellip; <a href=\"https:\/\/www.med.unc.edu\/wolberglab\/new-publication-in-blood-2\/\" aria-label=\"Read more about New publication in Blood\">Read more<\/a><\/p>\n","protected":false},"author":15383,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[],"class_list":["post-2685","post","type-post","status-publish","format-standard","hentry","category-news","odd"],"acf":[],"featured_image":false,"featured_image_medium":false,"featured_image_medium_large":false,"featured_image_large":false,"featured_image_thumbnail":false,"featured_image_alt":false,"category_details":[{"name":"News","link":"https:\/\/www.med.unc.edu\/wolberglab\/category\/news\/"}],"tag_details":[],"_links_to":[],"_links_to_target":[],"_links":{"self":[{"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/posts\/2685","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/users\/15383"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/comments?post=2685"}],"version-history":[{"count":0,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/posts\/2685\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/media?parent=2685"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/categories?post=2685"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/tags?post=2685"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}