title: Tumor necrosis factor-alpha as trigger of platelet activation in patients with heart failure.
abstract: 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.
authors.affiliation: University of Rome La Sapienza, Divisione IV Clinica Medica, Policlinico Umberto I, Viale del Policlinico, 00185, Rome, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Luciano
authors.initials: L
authors.lastname: De Biase
authors.forename: Luisa
authors.initials: L
authors.lastname: Lenti
authors.forename: Giuliano
authors.initials: G
authors.lastname: Tocci
authors.forename: Alessandra
authors.initials: A
authors.lastname: Brunelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Cangemi
authors.forename: Silvia
authors.initials: S
authors.lastname: Riondino
authors.forename: Susanna
authors.initials: S
authors.lastname: Grego
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: 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*
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D013928:Thromboxane A2; D003094:Collagen