title: Genes expressed in coronary thrombi are associated with ischemic time in patients with acute myocardial infarction.
abstract: BACKGROUND
  Reports on the content of aspirated coronary thrombi have until now mainly focused on cellular components. We investigated the genetic expression of selected mediators and proteases actively involved in the pathophysiological process of acute myocardial infarction in aspirated coronary thrombi.
  
  
  METHODS
  In this cross-sectional study, RNA from coronary thrombi in 67 subjects with acute myocardial infarction was isolated. Gene expression arrays of selected markers were performed by RT-PCR with relative quantification.
  
  
  RESULTS
  Twenty of 22 markers were expressed in >50% of the samples. The relative quantification of P-selectin correlated negatively to total ischemic time (p=0.01), while genes related to fibrinolysis (t-PA, u-PA, PAI-1), inflammation (PTX3, CXCL9, MCP-1, IL18, TNFα) and plaque instability (MMP-2 and TIMP-1) correlated positively to total ischemic time (all<0.05). Long ischemic time (>4.0 hours) associated with a relative reduction in the expression of P-selectin and a relative increase in the expression of t-PA, u-PA, PAI-1, PTX3, CXCL9, MCP-1, IL-18, TNFα, MMP-2 and TIMP-1. The presence of type 2 diabetes associated with 3.2-fold increased PAI-1 expression (adjusted p=0.033), while the presence of hypertension associated with about 50% reduction of IL-8 and TIMP-1. Smoking and overweight did not affect any markers.
  
  
  CONCLUSIONS
  The gene expression profile from coronary thrombi differed according to ischemic time, shown by reduced content of platelet markers and increased content of fibrinolytic, inflammatory and plaque instability mediators over time. Patients with type 2 diabetes showed increased expression of PAI-1, indicative of reduced fibrinolysis.
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Norway; Faculty of Medicine, University of Oslo, Norway. Electronic address: ragnhild.helseth@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Helseth
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Norway; Faculty of Medicine, University of Oslo, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Seljeflot
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Norway; Faculty of Medicine, University of Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Opstad
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Solheim
authors.affiliation: Department of Cardiology and Intensive Care, Wilhelminenhospital, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Freynhofer
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Norway; Faculty of Medicine, University of Oslo, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Arnesen
authors.affiliation: Department of Cardiology and Intensive Care, Wilhelminenhospital, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Huber
authors.affiliation: Department of Cardiology and Intensive Care, Wilhelminenhospital, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Weiss
mesh_terms: D000208:Acute Disease; D015331:Cohort Studies; D003328:Coronary Thrombosis / Q000150:complications / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology
keywords: Gene expression; Inflammation; Myocardial infarction; Thrombectomy; Thrombosis