Tangeretin regulates platelet function through inhibition of phosphoinositide 3-kinase and cyclic nucleotide signaling.
Arterioscler Thromb Vasc Biol
; 33(12): 2740-9, 2013 Dec.
Article
en En
| MEDLINE
| ID: mdl-24135020
ABSTRACT
OBJECTIVE:
Dietary flavonoids have long been appreciated in reducing cardiovascular disease risk factors, but their mechanisms of action are complex in nature. In this study, the effects of tangeretin, a dietary flavonoid, were explored on platelet function, signaling, and hemostasis. APPROACH ANDRESULTS:
Tangeretin inhibited agonist-induced human platelet activation in a concentration-dependent manner. It inhibited agonist-induced integrin αIIbß3 inside-out and outside-in signaling, intracellular calcium mobilization, and granule secretion. Tangeretin also inhibited human platelet adhesion and subsequent thrombus formation on collagen-coated surfaces under arterial flow conditions in vitro and reduced hemostasis in mice. Further characterization to explore the mechanism by which tangeretin inhibits platelet function revealed distinctive effects of platelet signaling. Tangeretin was found to inhibit phosphoinositide 3-kinase-mediated signaling and increase cGMP levels in platelets, although phosphodiesterase activity was unaffected. Consistent with increased cGMP levels, tangeretin increased the phosphorylation of vasodilator-stimulated phosphoprotein at S239.CONCLUSIONS:
This study provides support for the ability and mechanisms of action of dietary flavonoids to modulate platelet signaling and function, which may affect the risk of thrombotic disease.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trombosis
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Plaquetas
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Inhibidores de Agregación Plaquetaria
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Sistemas de Mensajero Secundario
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Activación Plaquetaria
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Flavonas
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Inhibidores de Proteínas Quinasas
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Inhibidores de las Quinasa Fosfoinosítidos-3
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Hemostasis
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido