Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-alpha.
OBJECTIVE
We studied the induction of monocytic inducible nitric oxide synthase expression and the tumour necrosis factor-alpha system in patients with congestive heart failure.


RESULTS
Forty-three congestive heart failure patients and 15 healthy subjects were studied. Antigenic tumour necrosis factor-alpha and its soluble receptors, measured by ELISA, were increased in chronic heart failure and the increase was related to the clinical severity of the syndrome (tumour necrosis factor-alpha from 8.2+/-5.2 in NYHA class II to 18.2+/-7.2 in class III and 26.9+/-13.2 pg. ml(-1)in class IV, P<0.0001 classes III and IV vs class II; soluble tumour necrosis factor receptor I from 1.0+/-0.2 in class II to 2.3+/-1.1 in class III and 5.5+/-3.2 ng. ml(-1)in class IV, P<0.0001 classes III and IV vs class II; soluble tumour necrosis factor receptor II from 2.7+/-0.7 in class II to 4.9+/-1.9 in class III and 8.4+/-5.0 ng. ml(-1)in class IV, P<0.002 classes III and IV vs class II). Monocytic inducible nitric oxide synthase assessed by Western blot, was expressed only in congestive heart failure patients (13 out of 43). The association among monocytic inducible nitric oxide synthase expression, tumour necrosis factor-alpha system activation, neurohormones and other clinical parameters was studied. The univariate logistic regression showed that inducible nitric oxide synthase expression was strictly associated with NYHA class (P<0.05), antigenic tumour necrosis factor-alpha (P<0.01) and its soluble receptors (P<0.05). The multivariate analysis showed that antigenic tumour necrosis factor-alpha was the only predictor for monocytic inducible nitric oxide synthase expression (P<0.05, RR=2.75, CI 1. 34-5.43).


CONCLUSIONS
Inducible nitric oxide synthase is expressed in circulating monocytes of patients with severe congestive heart failure. This phenomenon is linked to the activation of the tumour necrosis factor-alpha system.
Comini
L
L
Cardiovascular Pathophysiology Research Centre, Heart Failure Unit, 'Salvatore Maugeri' Foundation for Care and Research, Gussago, Italy.
Bachetti
T
T
Agnoletti
L
L
Gaia
G
G
Curello
S
S
Milanesi
B
B
Volterrani
M
M
Parrinello
G
G
Ceconi
C
C
Giordano
A
A
Corti
A
A
Ferrari
R
R
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology*; D018377:Neurotransmitter Agents / Q000097:blood; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015703:Antigens, CD; D015415:Biomarkers; D018377:Neurotransmitter Agents; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II