Platelets play a significant role in atherothrombosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is critically involved in regulation of LDL metabolism and interacts with platelet function. The effect of PCSK9 in platelet function is poorly understood. The authors sought to characterize platelet as a major source of PCSK9 and its role in atherothrombosis.
In a large cohort of patients with coronary artery disease (CAD), platelet count, platelet reactivity and platelet-derived PCSK9 release were analyzed. The role of platelet-PCSK9 on platelet and monocyte function was investigated in vitro.
Platelet count and hyper-reactivity correlated with plasma LDL in CAD. The circulating platelets express on their surface and release substantial amounts of PCSK9. Release of PCSK9 augmented platelet-dependent thrombosis, monocyte migration and differentiation into macrophages/foam cells. Platelets and PCSK9 accumulated in tissue derived from atherosclerotic carotid arteries in areas of macrophages. PCSK9 inhibition reduced platelet activation and platelet-dependent thrombo-inflammation.
The authors identified platelets as a major source of PCSK9 in CAD and may have an impact on LDL metabolism. Further, platelet-derived PCSK9 contributes to atherothrombosis, and inhibition of PCSK9 attenuates thrombo-inflammation which may contribute to the reported beneficial clinical effects.