Pigment epithelium-derived factor (PEDF) inhibits collagen-induced platelet activation by reducing intraplatelet nitrotyrosine levels

Abstract

We have recently found that pigment epithelium-derived factor (PEDF), a glycoprotein with a potent neuronal differentiating activity, not only inhibits platelet aggregation and P-selectin expression, but also suppresses occlusive thrombus formation in rats through its anti-oxidative properties. These findings suggest that PEDF may play a protective role against atherothrombosis. However, the underlying molecular mechanism by which PEDF inhibited platelet aggregation and activation in vitro is fully understood. Since nitric oxide (NO) suppresses platelet aggregation and activation, it is conceivable that PEDF could inhibit platelet activation by suppressing the inactivation of NO and subsequent formation of peroxynitrite via its anti-oxidative properties. In this study, we examined whether PEDF reduced intraplatelet nitrotyrosine levels, a marker of protein nitration by peroxynitrite, and subsequently suppressed platelet-derived growth factor-AB (PDGF-AB) production by collage-exposed platelets. PEDF was found to significantly reduce the collagen-elicited intraplatelet nitrotyrosine formation and PDGF-AB secretion by platelets. The present study demonstrated for the first time that PEDF could inhibit the collagen-induced platelet activation by suppressing nitrotyrosine formation. PEDF may inhibit the platelet activation by suppressing the inactivation of NO and subsequent formation of peroxynitrite via its anti-oxidative properties.