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

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-α–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. Methods and 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...