title: Soluble TNF receptors are associated with infarct size and ventricular dysfunction in ST-elevation myocardial infarction.
abstract: OBJECTIVE
  The aim of the study was to investigate circulating markers of apoptosis in relation to infarct size, left ventricular dysfunction and remodeling in an ST-elevation myocardial infarction (STEMI) population undergoing primary percutaneous coronary intervention (PCI).
  
  
  BACKGROUND
  Immediate re-opening of the acutely occluded infarct-related artery via primary PCI is the treatment of choice in STEMI to limit ischemia injury. However, the sudden re-initiation of blood flow can lead to a local acute inflammatory response with further endothelial and myocardial damage, so-called reperfusion injury. Apoptosis is suggested to be a key event in ischemia-reperfusion injury, resulting in LV-dysfunction, remodeling and heart failure.
  
  
  METHODS
  The present study is a prespecified substudy of the F.I.R.E. trial. We included 48 patients with STEMI undergoing primary PCI. Blood samples were collected prior to PCI and after 24 hours. Plasma was separated for later analysis of soluble tumor necrosis factor receptor (sTNFR) 1, sTNFR2, sFas and sFas ligand (sFasL) by ELISA. Infarct size, left ventricular (LV) dysfunction and remodeling were assessed by cardiac magnetic resonance imaging at five days and four months after STEMI.
  
  
  RESULTS
  The levels of sTNFR1 at 24 h as well as the relative increases in sTNFR1 and sTNFR2 over 24 h showed consistent and significant correlations with infarct size and LV-dysfunction at four months. Moreover, both sTNFRs correlated strongly with Troponin I and matrix metalloproteinase (MMP)-2 measurements. Soluble Fas and sFasL did not overall correlate with measures of infarct size or LV-dysfunction. None of the apoptosis markers correlated significantly with measures of remodeling.
  
  
  CONCLUSIONS
  In STEMI patients, circulating levels of sTNFR1 and sTNFR2 are associated with infarct size and LV dysfunction. This provides further evidence for the role of apoptosis in ischemia-reperfusion injury.
authors: Division of Cardiology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. lennart.nilsson@liu.se
authors: Lennart
authors: L
authors: Nilsson
authors: Aleksander
authors: A
authors: Szymanowski
authors: Eva
authors: E
authors: Swahn
authors: Lena
authors: L
authors: Jonasson
mesh_terms: D017209:Apoptosis; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism*; D019210:Troponin I / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology*; D020257:Ventricular Remodeling
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D019210:Troponin I; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2