Inhibitory Effect of Protocatechuic Acid on Platelet Aggregation Induced by High Shear Stress

Abstract

Background Platelet aggregation helps stop bleeding and thrombosis and blocks atherosclerosis, a cause of heart and cerebrovascular disease. Presently, bleeding and drug resistance are the most common side effects of clinically used antiplatelet drugsthus, it is particularly important to identify new antiplatelet drugs that can avoid or reduce these side effects. Method In this study,we used microfluidic chips in vitro to simulate the highly narrow bionic blood vessels of atherosclerosis to investigate the platelet aggregation on shear force-induced drug inhibition. Use flow cytometry to detect platelet activation markers（CD62P）.And thromboelasmograph and automatic coagulation analyzer were used to detect the coagulation function of blood after the action of protocatechuic acid. Results we found that platelets strongly aggregated after passing through the highly narrow microfluidic channel, and the aggregation can be inhibited by protocatechuic acid and CD42b but not by aspirin, tirofiban and other drugs.and protocatechuic acid inhibits platelet aggregation mainly by inhibiting interactions between platelet glycoprotein 1b (GPIb) and von Willebrand factor (vWF)，but does not activate platelets（ did not increase the expression of CD62P, a platelet activation marker）.In addition, protocatechuic acid did not significantly inhibit platelet aggregation induced by other endogenous agonists, such as collagen and ADP.It was found that the inhibitory effect of protocatechuic acid on platelet aggregation did not affect blood production, coagulation time, or coagulation function, reducing the drug resistance and frequent bleeding caused by aspirin. Conclusion Protocatechuic acid could selectively inhibit high shear force-induced platelet aggregation without affecting blood clotting function, However, the effect of the combination of the Protocatechuic acid and aspirin or other drugs remains to be studied. Therefore, we will conduct further studies on protocatechuic acid for new antithrombotic drugs, which can prevent thrombosis without affecting clotting time.