Tumor necrosis factor-α as trigger of platelet activation in patients with heart failure

Abstract

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-α (TNF-α) receptor expression, and serum thromboxane B2 and higher circulating levels of TNF-α than 20 healthy subjects. Coincubation of platelets from HF patients with an inhibitor of TNF-α receptors significantly reduced collagen-induced platelet aggregation. In vitro study demonstrated that TNF-α amplified the platelet response to collagen; this effect was inhibited by TNF-α receptor antagonist and inhibitors of arachidonic acid metabolism. This study showed that TNF-α behaves as a trigger of platelet activation through stimulation of the arachidonic acid pathway.