{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:26:47Z","timestamp":1790774807581,"version":"4.1.0"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"08","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>\n            Background\u2003Fibronectin splicing variant containing extra domain A (Fn-EDA), which is an endogenous ligand for Toll-like receptor 4 (TLR4), is present in negligible amounts in the plasma of healthy humans, but markedly elevated in patients with co-morbid conditions including diabetes and hyperlipidaemia, which are risk factors for myocardial infarction (MI). Very little is known about the role of Fn-EDA in the pathophysiology of acute MI under these co-morbid conditions.<\/jats:p><jats:p>\n            Materials and Methods\u2003We determined the role of Fn-EDA in myocardial ischaemia\/reperfusion (I\/R) injury in the hyperlipidaemic apolipoprotein E-deficient (ApoE\u2212\/\u2212) mice. Infarct size, plasma cardiac troponin I (cTnI) levels, intravascular thrombosis (CD41-positive), neutrophil infiltration (Ly6 B.2-positive), neutrophil extracellular traps (citrullinated H3-positive) and myocyte apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling-positive) were assessed in myocardial I\/R injury model (1-hour ischaemia\/23 hours of reperfusion).<\/jats:p><jats:p>\n            Results\u2003Irrespective of gender, Fn-EDA\u2212\/\u2212ApoE\u2212\/\u2212 mice exhibited smaller infarct size and decreased cTnI levels concomitant with reduced post-ischaemic intra-vascular thrombi, neutrophils influx, neutrophil extracellular traps and myocyte apoptosis (p\u2009&lt;\u20090.05 vs. ApoE\u2212\/\u2212 mice). Genetic deletion of TLR4 attenuated myocardial I\/R injury in ApoE\u2212\/\u2212 mice (p\u2009&lt;\u20090.05 vs. ApoE\u2212\/\u2212 mice), but did not further reduce in Fn-EDA\u2212\/\u2212 ApoE\u2212\/\u2212 mice suggesting that Fn-EDA requires TLR4 to mediate myocardial I\/R injury. Bone marrow transplantation experiments revealed that Fn-EDA exacerbates myocardial I\/R injury through TLR4 expressed on the haematopoietic cells. Infusion of a specific inhibitor of Fn-EDA, 15 minutes post-reperfusion, into ApoE\u2212\/\u2212 mice attenuated myocardial I\/R injury.<\/jats:p><jats:p>\n            Conclusion\u2003Fn-EDA exacerbates TLR4-dependent myocardial I\/R injury by promoting post-ischaemic thrombo-inflammatory response. Targeting Fn-EDA may reduce cardiac damage following coronary artery re-canalization after acute MI.<\/jats:p>","DOI":"10.1055\/s-0038-1661353","type":"journal-article","created":{"date-parts":[[2018,6,30]],"date-time":"2018-06-30T23:00:41Z","timestamp":1530399641000},"page":"1450-1460","source":"Crossref","is-referenced-by-count":26,"title":["Deletion of Extra Domain A of Fibronectin Reduces Acute Myocardial Ischaemia\/Reperfusion Injury in Hyperlipidaemic Mice by Limiting Thrombo-Inflammation"],"prefix":"10.1055","volume":"118","author":[{"given":"Mehul","family":"Chorawala","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Doddapattar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirav","family":"Dhanesha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2018,6,30]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0038-1661353.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T20:48:41Z","timestamp":1557175721000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0038-1661353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,30]]},"references-count":0,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2018,7,30]]},"published-print":{"date-parts":[[2018,8]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0038-1661353","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,30]]}}}