PMID- 9137215
OWN - NLM
STAT- MEDLINE
DCOM- 19970603
LR  - 20190708
IS  - 0735-1097 (Print)
IS  - 0735-1097 (Linking)
VI  - 29
IP  - 6
DP  - 1997 May
TI  - Plasma Fas ligand, an inducer of apoptosis, and plasma soluble Fas, an inhibitor 
      of apoptosis, in patients with chronic congestive heart failure.
PG  - 1214-20
AB  - OBJECTIVES: This study sought to examine plasma levels of soluble Fas/APO-1 
      receptor (sFas), an inhibitor of apoptosis, and soluble Fas ligand (sFas-L), an 
      inducer of apoptosis, and their relation to each other and to other clinical 
      variables, such as New York Heart Association functional class, tumor necrosis 
      factor (TNF) and interleukin-6 (IL-6) in congestive heart failure (CHF). 
      BACKGROUND: It has been recently reported that apoptotic cell death occurs in 
      myocytes of dogs with CHF. Hypoxia is frequently seen in advanced CHF and can 
      stimulate Fas/APO-1 receptors (Fas) to induce apoptosis in cultured myocytes. Fas 
      and Fas ligand (Fas-L) are cell-surface proteins and representative 
      apoptosis-signaling molecules. Fas on the cell membrane induces apoptosis when it 
      binds Fas-L or sFas-L. However, plasma sFas, a molecule lacking the transmembrane 
      domain of Fas, blocks apoptosis by inhibiting binding between Fas and Fas-L or 
      sFas-L on the cell membrane. At present, it is unknown whether plasma sFas-L and 
      plasma sFas increase in the presence of cardiac disease. METHODS: The study 
      included 70 patients (mean [+/-SEM] age 65 +/- 2 years, range 21 to 93) with 
      chronic CHF (coronary artery disease in 28, dilated cardiomyopathy in 27, 
      valvular heart disease in 15) and 62 age- and gender-matched normal control 
      subjects. Plasma levels of sFas, sFas-L, TNF-alpha and IL-6 were measured by 
      enzyme-linked immunosorbent assays using monoclonal anti-human antibodies. 
      RESULTS: There was no significant difference in sFas-L levels between normal 
      subjects and patients in functional classes I to IV; however, sFas increased with 
      severity of functional classification, independent of the underlying disease. 
      sFas levels were significantly higher even in patients in functional class II 
      than in normal subjects and those in functional class I, and were highest in 
      patients in functional class IV (normal subjects; 2.2 +/- 0.1 ng/ml; functional 
      class I: 2.2 +/- 0.2 ng/ml; functional class II: 3.1 +/- 0.2 ng/ml; functional 
      class III: 3.9 +/- 0.3 ng/ml; functional class IV: 5.1 +/- 0.6 ng/ml). Plasma 
      sFas levels were significantly higher in patients with elevated pulmonary artery 
      wedge pressure and a decresed cardiac index than in those with values in the 
      normal range. In patients in functional class IV, there was no significant 
      difference in plasma sFas levels between the survivors and non-survivors during 
      6-month follow-up. However, plasma levels of sFas tended to decrease in nine 
      patients with clinical improvement (baseline sFas: 5.2 +/- 0.8 ng/ml; 6-month 
      sFas: 4.3 +/- 0.5 ng/ml, p = 0.07) but were similar in patients with no change in 
      functional class. TNF-alpha and IL-6 were increased significantly only in 
      patients in functional class IV, as previously reported, but were not related to 
      sFas. CONCLUSIONS: We found elevated levels of plasma sFas and no increase in 
      plasma sFas-L in human CHF. The increase in sFas may play an important role in 
      the pathophysiologic mechanisms of CHF.
FAU - Nishigaki, K
AU  - Nishigaki K
AD  - Second Department of Internal Medicine, Gifu University School of Medicine, 
      Japan.
FAU - Minatoguchi, S
AU  - Minatoguchi S
FAU - Seishima, M
AU  - Seishima M
FAU - Asano, K
AU  - Asano K
FAU - Noda, T
AU  - Noda T
FAU - Yasuda, N
AU  - Yasuda N
FAU - Sano, H
AU  - Sano H
FAU - Kumada, H
AU  - Kumada H
FAU - Takemura, M
AU  - Takemura M
FAU - Noma, A
AU  - Noma A
FAU - Tanaka, T
AU  - Tanaka T
FAU - Watanabe, S
AU  - Watanabe S
FAU - Fujiwara, H
AU  - Fujiwara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Interleukin-6)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Aged
MH  - *Apoptosis
MH  - Cardiac Catheterization
MH  - Case-Control Studies
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fas Ligand Protein
MH  - Female
MH  - Follow-Up Studies
MH  - Heart Failure/*blood/diagnosis/physiopathology
MH  - Humans
MH  - Interleukin-6/blood
MH  - Male
MH  - Membrane Glycoproteins/*blood
MH  - Middle Aged
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 1997/05/01 00:00
MHDA- 1997/05/01 00:01
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 1997/05/01 00:01 [medline]
PHST- 1997/05/01 00:00 [entrez]
AID - S0735109797000557 [pii]
AID - 10.1016/s0735-1097(97)00055-7 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 1997 May;29(6):1214-20. doi: 10.1016/s0735-1097(97)00055-7.