title: The cardiac Fas (APO-1/CD95) Receptor/Fas ligand system : relation to diastolic wall stress in volume-overload hypertrophy in vivo and activation of the transcription factor AP-1 in cardiac myocytes.
abstract: BACKGROUND
  Fas (APO-1/CD95) is a transmembrane receptor belonging to the tumor necrosis factor receptor superfamily. Cross-linking of Fas by Fas ligand (FasL), a tumor necrosis factor-alpha-related cytokine, promotes apoptosis and/or transcription factor activation in a highly cell-type-specific manner. The biological consequences of Fas activation in cardiomyocytes and the regulation of Fas and FasL abundance in the myocardium in vivo remain largely unknown.
  
  
  RESULTS
  As shown by immunohistochemistry, Fas was expressed on the sarcolemma of cardiomyocytes in left ventricular tissue sections. Moreover, FasL was constitutively expressed in the myocardium and in isolated cardiomyocytes, as revealed by reverse transcription polymerase chain reaction and Western blotting. Left ventricular abundance of Fas but not FasL was upregulated in a rat model of compensated volume-overload hypertrophy and was closely related to diastolic but not systolic wall stress as determined by MRI. Cardiomyocyte apoptosis was not enhanced in volume-overload hypertrophy despite the increased expression of Fas and the presence of FasL in the myocardium. Moreover, injection of mice with an agonistic anti-Fas antibody promoted hepatocyte but not cardiomyocyte apoptosis in vivo. Stimulation of isolated cardiomyocytes with recombinant FasL promoted an activation of the transcription factor AP-1 as shown by electrophoretic mobility shift assays but did not induce cell death.
  
  
  CONCLUSIONS
  Fas and FasL are constitutively expressed in the myocardium and in cardiomyocytes. Myocardial expression of Fas is closely related to diastolic loading conditions in vivo. Signaling pathways emanating from Fas are coupled to an activation of the transcription factor AP-1 in cardiomyocytes.
authors.affiliation: Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: K C
authors.initials: KC
authors.lastname: Wollert
authors.forename: J
authors.initials: J
authors.lastname: Heineke
authors.forename: J
authors.initials: J
authors.lastname: Westermann
authors.forename: M
authors.initials: M
authors.lastname: Lüdde
authors.forename: B
authors.initials: B
authors.lastname: Fiedler
authors.forename: W
authors.initials: W
authors.lastname: Zierhut
authors.forename: D
authors.initials: D
authors.lastname: Laurent
authors.forename: M K
authors.initials: MK
authors.lastname: Bauer
authors.forename: K
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: H
authors.initials: H
authors.lastname: Drexler
mesh_terms: D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D053222:Fas Ligand Protein; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000502:physiology; D019014:fas Receptor / Q000096:biosynthesis*
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D019014:fas Receptor