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Associations between circulating proteins and corresponding genes expressed in coronary thrombi in patients with acute myocardial infarction
Oslo Univ Hosp Ulleval, Ctr Clin Heart Res, Dept Cardiol, N-0424 Oslo, Norway.;Univ Oslo, Fac Med, Oslo, Norway..
Wilhelminen Hosp, Dept Cardiol & Intens Care Med, Vienna, Austria..
Oslo Univ Hosp Ulleval, Ctr Clin Heart Res, Dept Cardiol, N-0424 Oslo, Norway.;Univ Oslo, Fac Med, Oslo, Norway..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
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2015 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 6, 1240-1244 p.Article in journal (Refereed) Published
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Abstract [en]

Introduction: Several genes are expressed in aspirated coronary thrombi in acute myocardial infarction (AMI), exhibiting dynamic changes along ischemic time. Whether soluble biomarkers reflect the local gene environment and ischemic time is unclear. We explored whether circulating biomarkers were associated with corresponding coronary thrombi genes and total ischemic time. Material and methods: In 33 AMI patients undergoing percutaneous coronary intervention (PCI), blood samples were collected within 6-24 h for markers related to plaque rupture (metalloproteinase 9, tissue inhibitor of metalloproteinases 1), platelet and endothelial cell activation (P-selectin, CD40 ligand, PAR-1), hemostasis (tissue factor, tissue plasminogen activator, plasminogen activator inhibitor 1, free and total tissue factor pathway inhibitor, D-dimer, prothrombin fragment 1 + 2), inflammation (interleukin 8 and 18, fractalkine, monocyte chemoattractant protein 1 (MCP-1), CXCL1, pentraxin 3, myeloperoxidase) and galectin 3, caspase 8 and epidermal growth factor (EGF). Laboratory analyses were performed by Proximity Extension Assay (Proseek Multiplex CVD I-96 (x 96)), ELISAs and RT-PCR. Results: Only circulating P-selectin correlated to the corresponding P-selectin gene expression in thrombi (r = 0.530, p = 0.002). Plasma galectin 3, fractalkine, MCP-1 and caspase 8 correlated inversely to ischemic time (r = -0.38-0.50, all p < 0.05), while plasma MCP-1, galectin 3 and EGF were higher at short (<= 4 h) vs. long (>4 h) ischemic time (all p < 0.05). Conclusions: The dynamic changes in circulating mediators along ischemic time were not reflected in the profile of locally expressed genes. These observations indicate a locally confined milieu within the site of atherothrombosis, which may be important for selective therapy.

Place, publisher, year, edition, pages
2015. Vol. 136, no 6, 1240-1244 p.
Keyword [en]
Acute myocardial infarction, Coronary artery disease, Thrombus, Gene expression, Biomarkers
National Category
Hematology Cardiac and Cardiovascular Systems
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URN: urn:nbn:se:uu:diva-274702DOI: 10.1016/j.thromres.2015.10.005ISI: 000366712800036OAI: oai:DiVA.org:uu-274702DiVA: diva2:900489
Available from: 2016-02-04 Created: 2016-01-25 Last updated: 2017-11-30Bibliographically approved

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Siegbahn, Agneta

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