title: Etanercept or intravenous immunoglobulin attenuates expression of genes involved in post-myocardial infarction remodeling.
abstract: OBJECTIVE
  Persistently elevated levels of inflammatory cytokines such as tumor necrosis factor (TNF)alpha after acute myocardial infarction (MI) may contribute to maladaptive ventricular remodeling. The aim of the present study was to examine the effects of immunomodulatory therapy with recombinant soluble TNF receptor (TNFR:Fc) or intravenous immunoglobulin (IVIg) on left and right ventricular post-MI remodeling in rats.
  
  
  RESULTS
  Adult male Sprague-Dawley rats were subjected to MI by left coronary artery ligation and randomized to treatment with vehicle, TNFR:Fc, or IVIg and sacrificed after 7 days. The main findings were that: (i) TNFR:Fc- and IVIg-treated rats developed less right ventricular (RV) hypertrophy compared to vehicle-treated controls. (ii) LV and arterial pressures in post-MI rats were not affected by the TNFR:Fc or IVIg treatment. (iii) As determined by real-time RT-PCR, both treatments reduced the expression of the hypertrophy-related genes, atrial natriuretic peptide and the ratio of beta/alpha-myosin heavy chains, and genes related to extracellular matrix remodeling (i.e., collagens I and III, matrix metalloproteinase [MMP]-2 and its tissue inhibitor TIMP-1) in the non-ischemic segment of LV and, in particular, in the RV. (iv) Treatment with IVIg, but not TNFR:Fc, reduced MMP-2 zymographic activity in the RV and the expression of genes for TNFalpha and monocyte chemoattractant protein-1.
  
  
  CONCLUSIONS
  Therapy targeted directly against TNFalpha (i.e., TNFR:Fc) and a more general immunomodulatory approach (i.e., IVIg) in the acute phase of MI attenuates the cardiac remodeling process and expression of genes that are involved. These findings raise the possibility that initiation of immunomodulatory therapy post-MI could be beneficial in preventing the later development of heart failure.
authors.affiliation: Department of Medicine, Division of Cardiology, University of California, San Diego, Medical Center, 200 W Arbor Drive, San Diego, California, CA 92103-8411, USA.
authors.forename: Devorah
authors.initials: D
authors.lastname: Gurantz
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Ottar V
authors.initials: OV
authors.lastname: Lunde
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Omens
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Cristina D
authors.initials: CD
authors.lastname: Moore
authors.forename: John
authors.initials: J
authors.lastname: Kjekshus
authors.forename: Barry H
authors.initials: BH
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D003094:Collagen / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D000068800:Etanercept; D005355:Fibrosis; D005786:Gene Expression Regulation; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000627:therapeutic use*; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D016207:Cytokines; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D000068800:Etanercept