title: Escape from cardiomyocyte apoptosis by enterovirus persistence due to elevated soluble Fas-receptors.
abstract: BACKGROUND
  Apoptosis causes loss of contractile cardiomyocytes in inflammatory heart disease. Despite recent examinations, the influence of virus infection on apoptosis remained ill-defined.
  
  
  METHODS
  Apoptosis was assessed in left ventricular endomyocardial biopsies by the TUNEL method frompatients with chronic myocarditis and adeno-, cytomegalo- and enterovirus persistence. Soluble Fas-ligands, sFas-receptors, TNF-alpha, IL-6, IL-10 and IFN-gamma were measured using ELISA technique.
  
  
  RESULTS
  Elevated (P < 0.05) rates of apoptosis were found in patients with autoimmune myocarditis. Apoptosis was increased (P < 0.05) in the case of cytomegalovirus persistence, but not significantly increased in the presence of adenoviral genome. No evidence for apoptosis, but elevated concentrations of soluble Fas-receptors were found only in the case of enterovirus persistence. In turn, elevated percentages of apoptosis and normal soluble Fas-receptor concentrations were found in patients with chronic myocarditis. Serum levels of soluble Fas-ligands, TNF-alpha, IL-6, IL-10 and IFN-gamma did not predict changes in TUNEL-positivity.
  
  
  CONCLUSIONS
  Escape mechanisms to protect cardiomyocytes from apoptosis are yet not known for enterovirus infections. Soluble Fas-receptors have to be considered to counteract binding of soluble Fas-ligands that results in the blockade of apoptosis induction. It is a new finding that soluble Fasreceptors were elevated in the presence of enterovirus genome in the heart. Inhibition of apoptosis can impair virus clearing and prolong its replication with a potential worse outcome. In turn, sufficient protection from apoptosis in autoimmune myocarditis should reduce loss of cardiomyocytes. Therefore, the interaction of the Fas components could provide a new therapeutic target in myocarditis.
authors.affiliation: University of Marburg/Lahn, Department of Internal Medicine Cardiology, Baldingerstrasse, 35033 Marburg, Germany. alter@mailer.uni-marburg.de
authors.forename: P
authors.initials: P
authors.lastname: Alter
authors.forename: B
authors.initials: B
authors.lastname: Maisch
mesh_terms: D000257:Adenoviridae Infections / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology*; D001327:Autoimmune Diseases / Q000473:pathology; D001706:Biopsy; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis; D003586:Cytomegalovirus Infections / Q000473:pathology*; D004699:Endocardium / Q000473:pathology* / Q000821:virology; D004770:Enterovirus / Q000502:physiology*; D004769:Enterovirus Infections / Q000473:pathology*; D053222:Fas Ligand Protein; D006801:Humans; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000032:analysis; D009205:Myocarditis / Q000473:pathology* / Q000821:virology; D009206:Myocardium / Q000473:pathology*; D017735:Virus Latency / Q000502:physiology*; D019014:fas Receptor / Q000032:analysis*
chemical_list: D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor