Proinflammatory cytokine activation is linked to apoptotic mediator, soluble Fas level in patients with chronic heart failure.
The Fas/Fas Ligand system is a major apoptosis signaling pathway that is up-regulated in patients with chronic heart failure (CHF). Serum soluble Fas (sFas) levels increase in proportion to the CHF severity and may have prognostic value, therefore, sFas is a promising biomarker of heart failure. In this study, we attempted to identify the determinants of sFas levels in patients with CHF. Serum levels of tumor necrosis factor (TNF)-α and its soluble receptors (sTNF-R1 & sTNF-R2), interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), glycoprotein (gp)130, and sFas were measured in 106 patients with CHF and 39 controls. All subjects performed a symptom-limited cycle ergometer exercise test with expired gas analysis. CHF patients had higher levels of TNF-α, sTNF-R1, sTNF-R2, IL-6, and gp130. Serum levels of sFas (controls versus CHF; 2.60 ± 0.88 versus 3.38 ± 1.23 ng/mL, P = 0.0004) were higher in CHF. On univariate analysis, age (P = 0.0003), NYHA functional class (P = 0.0012), peak VO<inf>2</inf> (P < 0.0001), plasma norepinephrine (P = 0.0013), log IL-6 (P < 0.0001), log TNF-α (P = 0.0002), log sTNF-R1 (P < 0.0001), and log TNF-R2 (P < 0.0001) were significantly related to log sFas levels. Multivariate analysis showed that age and log IL-6 and log sTNF-R1 levels were independently associated with log sFas levels (overall R = 0.603, P < 0.0001). Serum levels of sFas were increased in patients with CHF, and age and serum IL-6 and sTNF-R1 levels were independent determinants of sFas levels. These data suggest that proinflammatory cytokine activation is linked to the Fas/Fas Ligand system in patients with CHF.
Kinugawa Cardiology Clinic, Osaka, Japan.
Toru
T
Kinugawa
Masahiko
M
Kato
Kazuhiro
K
Yamamoto
Ichiro
I
Hisatome
Ryuji
R
Nohara
D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood*; D005080:Exercise Test; D053222:Fas Ligand Protein / Q000097:blood*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019947:Receptors, Interleukin-6 / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012016:Reference Values; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation / Q000502:physiology; D019014:fas Receptor / Q000097:blood*
D016207:Cytokines; C491901:FAS protein, human; D053222:Fas Ligand Protein; D006023:Glycoproteins; C508603:IL6R protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C480482:glycoprotein 130, human