Paclitaxel exerts antiplatelet and antithrombotic activities: Additional benefit from use of paclitaxel-coated balloons and -eluting stents in coronary revascularization and prevention of in-stent restenosis. Issue 225 (May 2023)

• Record Type: Journal Article
• Authors: Lin, Kuan-Hung; Li, Jiun-Yi; Chen, Ray-Jade; Chen, Ting-Yu; Hsu, Shao-Hsuan; Wang, Hsueh-Hsiao; Peng, Hsien-Yu; Sun, Yu-Yo; Lu, Wan-Jung
• Is Part Of: Thrombosis research. Issue 225(2023)
• Page Start: 63
• Page End: 72
• Publication Date: 2023-05
• Subjects: GPVI -- Paclitaxel -- Platelet activation -- thrombus formation; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2023.03.017
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: 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. Methods and results: 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. Conclusion: 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. Graphical abstract: Unlabelled Image Highlights: Platelet activation is involved in thrombosis and in-stent restenosis. Paclitaxel-coated balloon and -eluting stent used for coronary revascularization Paclitaxel exerts antiplatelet and antithrombotic activities. Paclitaxel's antiplatelet effects also contribute to preventing in-stent restenosis.