title: Alterations in the interleukin-1/interleukin-1 receptor antagonist balance modulate cardiac remodeling following myocardial infarction in the mouse.
abstract: BACKGROUND
  Healing after acute myocardial infarction (AMI) is characterized by an intense inflammatory response and increased Interleukin-1 (IL-1) tissue activity. Genetically engineered mice lacking the IL-1 receptor (IL-1R1-/-, not responsive to IL-1) or the IL-1 receptor antagonist (IL-1Ra, enhanced response to IL-1) have an altered IL-1/IL-1Ra balance that we hypothesize modulates infarct healing and cardiac remodeling after AMI.
  
  
  METHODS
  IL-1R1-/- and IL-1Ra-/- male mice and their correspondent wild-types (WT) were subjected to permanent coronary artery ligation or sham surgery. Infarct size (trichrome scar size), apoptotic cell death (TUNEL) and left ventricular (LV) dimensions and function (echocardiography) were measured prior to and 7 days after surgery.
  
  
  RESULTS
  When compared with the corresponding WT, IL-1R1-/- mice had significantly smaller infarcts (-25%), less cardiomyocyte apoptosis (-50%), and reduced LV enlargement (LV end-diastolic diameter increase [LVEDD], -20%) and dysfunction (LV ejection fraction [LVEF] decrease, -50%), whereas IL-1Ra-/- mice had significantly larger infarcts (+75%), more apoptosis (5-fold increase), and more severe LV enlargement (LVEDD increase,+30%) and dysfunction (LVEF decrease, +70%)(all P values <0.05).
  
  
  CONCLUSIONS
  An imbalance in IL-1/IL-1Ra signaling at the IL-1R1 level modulates the severity of cardiac remodeling after AMI in the mouse, with reduced IL-1R1 signaling providing protection and unopposed IL-1R1 signaling providing harm.
authors.affiliation: Victoria Johnson Research Laboratory and VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia, United States of America. aabbate@mcvh-vcu.edu
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
authors.forename: Fadi N
authors.initials: FN
authors.lastname: Salloum
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Van Tassell
authors.forename: Elena
authors.initials: E
authors.lastname: Vecile
authors.forename: Stefano
authors.initials: S
authors.lastname: Toldo
authors.forename: Ignacio
authors.initials: I
authors.lastname: Seropian
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mezzaroma
authors.forename: Aldo
authors.initials: A
authors.lastname: Dobrina
mesh_terms: D000818:Animals; D017209:Apoptosis; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000172:deficiency / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology* / Q000601:surgery; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D013599:Systole; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1