Ongoing myocardial damage in chronic heart failure is related to activated tumor necrosis factor and Fas/Fas ligand system.
BACKGROUND
Elevated concentrations of cardiac troponin T and heart-type fatty acid-binding protein (H-FABP) identify patients with chronic heart failure (CHF) and ongoing myocardial damage (OMD) who are at increased risk for future cardiac events. Cardiomyocyte necrosis and/or apoptosis via activated tumor necrosis factor (TNF) and the Fas/Fas ligand (FasL) system may be related to the development of OMD.


RESULTS
The serum concentrations of H-FABP, a sensitive marker of membrane damage of cardiomyocytes, soluble Fas (sFas) and TNF-alpha were measured in 38 patients with CHF. The concentrations of H-FABP, TNF-alpha and s-Fas in patients with New York Heart Association (NYHA) III + IV were all significantly higher than in those patients in NYHA II (H-FABP; III + IV 9.3+/-5.9 vs II 5.1+/-1.8 ng/ml, p=0.003, TNF-alpha; III + IV 10.5+/-3.8 vs II 8.0+/-2.7 pg/ml, p=0.02, sFas; III + IV 3.36+/-1.37 vs II 2.58 +/-0.84 ng/ml, p=0.03). Increased concentrations of H-FABP significantly correlated with the concentrations of TNF- alpha (r=0.57, p=0.0001) and sFas (r=0.69, p<0.0001), independent of renal function.


CONCLUSIONS
OMD detected by H-FABP, a marker of membrane damage, is related to activated TNF and the Fas/FasL system, which suggests a pathophysiological role of cardiomyocyte necrosis and/or apoptosis in patients with worsening heart failure.
Division of Cardiology, Department of Medicine, Tokyo Metropolitan Komagome Hospital, Japan.
Koichi
K
Setsuta
Yoshihiko
Y
Seino
Takeshi
T
Ogawa
Toshiaki
T
Ohtsuka
Kohji
K
Seimiya
Teruo
T
Takano
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D053222:Fas Ligand Protein; D050556:Fatty Acid-Binding Proteins; D005260:Female; D006333:Heart Failure / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D019014:fas Receptor / Q000097:blood*
D015415:Biomarkers; D002352:Carrier Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D050556:Fatty Acid-Binding Proteins; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor