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http://140.112.115.32:8080/ir/handle/987654321/2813
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| Title: | 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 |
| 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 |
| Contributors: | 視光學系 |
| Keywords: | GPVI;Paclitaxel;Platelet activation;thrombus formation |
| Date: | 2023-05-01 |
| Issue Date: | 2025-08-11 14:44:20 (UTC+8) |
| 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. |
| Relation: | Thrombosis Research, 225, 63-72. https://doi.org/10.1016/j.thromres.2023.03.017 |
| Appears in Collections: | [視光學系] 期刊論文
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