Associations Between Circulating Proteins and Corresponding Genes Expressed in Coronary Thrombi in Patients With Acute Myocardial Infarction

Thromb Res. 2015 Dec;136(6):1240-4. doi: 10.1016/j.thromres.2015.10.005. Epub 2015 Oct 8.

Abstract

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 6-24h 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.

Keywords: Acute myocardial infarction; Biomarkers; Coronary artery disease; Gene expression; Thrombus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Blood Platelets / metabolism
  • Caspase 8 / blood
  • Chemokine CCL2 / blood
  • Chemokine CX3CL1 / blood
  • Cohort Studies
  • Coronary Thrombosis / blood*
  • Epidermal Growth Factor / blood
  • Female
  • Galectin 3 / blood
  • Gene Expression Regulation*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • P-Selectin / blood
  • Percutaneous Coronary Intervention
  • Thrombosis / blood*
  • Time Factors

Substances

  • Biomarkers
  • CCL2 protein, human
  • CX3CL1 protein, human
  • Chemokine CCL2
  • Chemokine CX3CL1
  • Galectin 3
  • P-Selectin
  • galectin-3, human
  • Epidermal Growth Factor
  • CASP8 protein, human
  • Caspase 8