紫杉醇是一种微管稳定药物，用于治疗多种癌症，包括卵巢癌和乳腺癌。由于其对血管平滑肌细胞的抗增殖作用，球囊和支架上涂有紫杉醇，用于冠状动脉重建和支架内再狭窄（ISR）的预防。然而，支架内再狭窄的机制很复杂。血小板活化是经皮冠状动脉介入后ISR的主要原因之一。尽管已经注意到紫杉醇对兔血小板的抗血小板活化作用，但其对血小板的影响仍不清楚。本研究调查了紫杉醇是否在人血小板中表现出抗血小板活性。紫杉醇抑制胶原蛋白诱导的血小板聚集，但不抑制凝血酶、花生四烯酸或U46619诱导的血小板聚集，提示紫杉醇对抑制胶原蛋白诱发的血小板活化更为敏感。此外，紫杉醇阻断了胶原受体糖蛋白（GP）VI下游信号分子，包括Lyn、Fyn、PLCγ2、PKC、Akt和MAPK。然而，紫杉醇不直接与GPVI结合引起GPVI剥脱，如表面等离子共振和流式细胞术所检测，表明紫杉醇可能干扰GPVI下游信号分子，如Lyn和Fyn。紫杉醇还防止了由胶原蛋白和低龙蝎素剂量引起的颗粒释放和GPIIbIIIa的激活。此外，紫杉醇减轻了肺血栓形成，并延缓了肠系膜微血管中血小板血栓形成，而对止血性没有明显影响。因此，紫杉醇具有抗血小板和抗血栓作用，因此在用于药物包被球囊和药物洗脱支架进行冠状动脉重建和ISR预防时，紫杉醇除了其抗增殖效应外，也可能提供额外的益处。版权所有 © 2023 Elsevier Ltd.

Paclitaxel is a microtubule-stabilizing drug used to treat several types of cancer, including ovarian and breast cancer. Because of its antiproliferative effect on vascular smooth muscle cells, balloons and stents are coated with paclitaxel for use in coronary revascularization and prevention of in-stent restenosis (ISR). However, mechanisms underlying ISR are complicated. Platelet activation is one of the major causes of ISR after percutaneous coronary intervention. Although the antiplatelet activity of paclitaxel was noted in rabbit platelets, the effect of paclitaxel on platelets remains unclear. This study investigated whether paclitaxel exhibits antiplatelet activity in human platelets.Paclitaxel inhibited platelet aggregation induced by collagen but not that induced by thrombin, arachidonic acid, or U46619, suggesting that paclitaxel is more sensitive to the inhibition of collagen-induced platelet activation. Moreover, paclitaxel blocked collagen receptor glycoprotein (GP) VI downstream signaling molecules, including Lyn, Fyn, PLCγ2, PKC, Akt, and MAPKs. However, paclitaxel did not directly bind to GPVI and cause GPVI shedding, as detected by surface plasmon resonance and flow cytometry, respectively, indicating that paclitaxel may interfere with GPVI downstream signaling molecules, such as Lyn and Fyn. Paclitaxel also prevented granule release and GPIIbIIIa activation induced by collagen and low convulxin doses. Moreover, paclitaxel attenuated pulmonary thrombosis and delayed platelet thrombus formation in mesenteric microvessels without significantly affecting hemostasis.Paclitaxel exerts antiplatelet and antithrombotic effects. Thus, paclitaxel may provide additional benefits beyond its antiproliferative effect when used in drug-coated balloons and drug-eluting stents for coronary revascularization and prevention of ISR.Copyright © 2023. Published by Elsevier Ltd.