Thromboxane A(2) promotes soluble CD40 ligand release from human platelets

Atherosclerosis
Yukiko EnomotoOsamu Kozawa

Abstract

The plasma level of soluble CD40 ligand (sCD40L), which induces pro-inflammatory and pro-atherogenic responses, is known to be elevated in atherosclerotic patients. In this study, we investigated the mechanism of sCD40L release from human platelets, focusing on the involvement of thromboxane (TX) A(2). We measured sCD40L release and TXA(2) production induced by ristocetin, an activator of GPIb/IX/V, from human platelets in vitro. Moreover, plasma sCD40L and TXA(2) levels in the 10 patients with severe carotid artery stenosis who were not taking any anti-platelet medicines were measured and compared with those obtained from non-atherosclerotic controls. Ristocetin significantly promoted sCD40L release and TXA(2) generation from platelets in vitro. Aspirin and SC-560, a cyclooxygenase-1 inhibitor, suppressed the ristocetin-induced sCD40L release from platelets in parallel with TXA(2) production. Ozagrel, a TXA(2) synthase inhibitor and PTXA(2), a thromboxane receptor (TP) antagonist also suppressed sCD40L release. U46619, a TP agonist, reversed the suppressive effect of aspirin on sCD40L release. In vivo, plasma levels of sCD40L and TXA(2) in the patients were significantly higher than those in controls. Elevated plasma levels of...Continue Reading

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Citations

Feb 16, 2011·Biomarkers in Medicine·Karsten SchrörThomas Hohlfeld
Jul 24, 2012·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Tomoaki DoiShinji Ogura
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Jan 26, 2021·Atherosclerosis·Tiago Pereira-da-SilvaMiguel Mota Carmo

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