Tumor necrosis factor-alpha as trigger of platelet activation in patients with heart failure.
The clinical history of patients with heart failure (HF) is complicated by arterial thromboembolism. Platelet activation is reported in this population, but the underlying mechanism has not been clarified. Forty-two patients with HF scored according to New York Heart Association (NYHA) classification had higher levels of collagen-induced platelet aggregation, platelet tumor necrosis factor-alpha (TNF-alpha) receptor expression, and serum thromboxane B2 and higher circulating levels of TNF-alpha than 20 healthy subjects. Coincubation of platelets from HF patients with an inhibitor of TNF-alpha receptors significantly reduced collagen-induced platelet aggregation. In vitro study demonstrated that TNF-alpha amplified the platelet response to collagen; this effect was inhibited by TNF-alpha receptor antagonist and inhibitors of arachidonic acid metabolism. This study showed that TNF-alpha behaves as a trigger of platelet activation through stimulation of the arachidonic acid pathway.
Pignatelli
Pasquale
P
University of Rome La Sapienza, Divisione IV Clinica Medica, Policlinico Umberto I, Viale del Policlinico, 00185, Rome, Italy.
De Biase
Luciano
L
Lenti
Luisa
L
Tocci
Giuliano
G
Brunelli
Alessandra
A
Cangemi
Roberto
R
Riondino
Silvia
S
Grego
Susanna
S
Volpe
Massimo
M
Violi
Francesco
F
D000368:Aged; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology; D016022:Case-Control Studies; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D013928:Thromboxane A2; D003094:Collagen