title: Associations between circulating proteins and corresponding genes expressed in coronary thrombi in patients with acute myocardial infarction.
abstract: BACKGROUND
  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.
  
  
  METHODS
  In 33 AMI patients undergoing percutaneous coronary intervention (PCI), blood samples were collected within 6-24h 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 × 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 (>4h) 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.
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: ragnhild.helseth@gmail.com.
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Helseth
authors.affiliation: Department of Cardiology and Intensive Care Medicine, Wilhelminen Hospital, Vienna,Austria.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Weiss
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Trine Baur
authors.initials: TB
authors.lastname: Opstad
authors.affiliation: Department of Medical Sciences, Clinical Chemistry, Uppsala University, University Hospital Uppsala, Uppsala, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Solheim
authors.affiliation: Department of Cardiology and Intensive Care Medicine, Wilhelminen Hospital, Vienna,Austria.
authors.forename: Matthias K
authors.initials: MK
authors.lastname: Freynhofer
authors.affiliation: Department of Cardiology and Intensive Care Medicine, Wilhelminen Hospital, Vienna,Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Arnesen
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Seljeflot
authors.initials: S
authors.lastname: Seljeflot
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism; D001798:Blood Proteins; D053181:Caspase 8 / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D054428:Chemokine CX3CL1 / Q000097:blood; D015331:Cohort Studies; D003328:Coronary Thrombosis / Q000097:blood*; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D037502:Galectin 3 / Q000097:blood; D037161:Galectins; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D019007:P-Selectin / Q000097:blood; D062645:Percutaneous Coronary Intervention; D013927:Thrombosis / Q000097:blood*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; C111835:CCL2 protein, human; C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; D019007:P-Selectin; D004815:Epidermal Growth Factor; C505530:CASP8 protein, human; D053181:Caspase 8
keywords: Acute myocardial infarction; Biomarkers; Coronary artery disease; Gene expression; Thrombus