Microfluidic analysis of epigallocatechin gallate selectively inhibiting shear-induced platelet aggregation under pathological high shear stress.

Abstract

ObjectivesTo investigate the mechanism underlying the inhibitory effect of epigallocatechin gallate (EGCG) on shear-induced platelet aggregation(SIPA) and activation.MethodsUsing an 80% eccentric stenotic microfluidic chip, we simulated physiological (1500 s^-1) and pathological high shear rates (4500 s^-1 and 9000 s^-1). Whole blood samples preincubated with EGCG (25-200 μM) were perfused through the chips. SIPA was quantified by real-time image analysis, and platelet activation was measured by flow cytometry for CD62P (P-selectin) and PAC-1 expression. The potential mechanism was probed using Ristocetin-induced activation.ResultsEGCG demonstrated a potent, concentration-dependent inhibition of SIPA and platelet activation at both 4500 s^-1 and 9000 s^-1, evidenced by reduced platelet aggregate coverage and lower CD62P/PAC-1 expression. The inhibitory effect was confirmed to be mediated through the von Willebrand factor (vWF)-GPIbα pathway, as EGCG also suppressed Ristocetin-induced platelet activation.ConclusionThis study offers systematic microfluidic evidence that EGCG exerts a concentration-dependent, selective inhibition of pathological SIPA and activation at 4500 s^-1 and 9000 s^-1, while exerting no significant effect on platelet aggregation function under physiological shear rate (1500 s^-1). By targeting the vWF-GPIbα axis without affecting coagulation, EGCG emerges as a promising prototype for developing novel, bleeding-risk-free antiplatelet therapies.