Human milk oligosaccharide, 2′-Fucosyllactose, attenuates platelet activation in arterial thrombosis

Abstract

A schematic model of GPVI-mediated platelet activation pathway inhibited by 2′-Fucosyllactose (2′-FL). 2′-FL inhibits multiple aspects of the GPVI activation pathway, including Syk signalosome, granule secretion, calcium mobilization, integrin αIIbβ3 activation and aggregation. GPVI, glycoprotein VI; IP3, inositol 1,4,5-trisphosphate; PLC, phospholipase C; Syk, spleen tyrosine kinase. • 2′-FL effectively reduces the platelet thrombus formation in vitro. • Oral administration of 2′-FL has immediate benefits in thrombus formation and a mouse model of ischemia/reperfusion-induced stroke in vivo. The ingestion of supplemental human milk oligosaccharides (HMOs) is associated with a lower risk of inflammatory diseases and infections. However, whether HMOs play an important role in regulating platelet aggregation and thrombus formation remains unclear. The current study aimed to investigate the antiplatelet and antithrombotic effects of HMOs. Among all HMOs, 2′-fucosyllactose (2′-FL) could significantly inhibit collagen-related peptide-induced platelet aggregation, granule secretion, and intracellular calcium mobilization. Notably, the inhibitory effect of 2′-FL was associated with the inhibition of glycoprotein VI-mediated platelet signal transduction during cell activation. In accordance with antiplatelet activities, the oral administration of 2′-FL was effective in blocking ferric chloride-induced arterial thrombus formation in vivo without prolonging bleeding time. Studies using a mouse model of ischemia-/reperfusion-induced stroke revealed that treatment with 2′-FL reduced infarct volume in stroke. Hence, the therapeutic potential of 2′-FL supplementation may play a protective role against thrombotic diseases.