Department of Pathology and Pathophysiology, Basic Medical School of Wuhan University, Wuhan, China.
Pharmacology. 2010;85(3):136-45. doi: 10.1159/000280587. Epub 2010 Feb 9.
The long-term success of percutaneous coronary interventions has been limited by restenosis. Therefore, local delivery of paclitaxel, an antiproliferative agent, using drug-eluting stents has been applied to prevent in-stent restenosis. However, paclitaxel not only inhibits smooth muscle cell proliferation, but also delays re-endothelialization of the damaged site, which may cause potentially life-threatening cardiovascular adverse events, especially late and very late stent thrombosis. We investigated the role of paclitaxel in endothelial cell line ECV304 adhesion and migration. Accordingly, changes in vasodilator-stimulated phosphoprotein protein (VASP) phosphorylation and cAMP-dependent protein kinase activity during ECV304 cell detachment and reattachment were investigated as well. The results showed that the decrease in VASP phosphorylation paralleled the inhibition of cAMP-dependent protein kinase (PKA) activity in the presence of paclitaxel (10 microg/l). Cell adhesion assay and two- and three-dimensional cell migration assays were performed to determine the effect of paclitaxel on the adhesion and migration of ECV304 cells. Paclitaxel significantly suppresses the adhesion (p < 0.05) and migration of ECV304 cells (p < 0.05). These data suggest that the inhibitory effect of paclitaxel may be produced by decreasing the phosphorylation of VASP via inhibition of PKA activity during ECV304 cell adhesion and migration.
经皮冠状动脉介入治疗的长期疗效受到再狭窄的限制。因此，应用载紫杉醇药物洗脱支架局部递送抗增殖药物紫杉醇，以预防支架内再狭窄。然而，紫杉醇不仅抑制平滑肌细胞增殖，而且延迟损伤部位的再内皮化，这可能导致潜在的危及生命的心血管不良事件，尤其是晚期和极晚期支架血栓形成。我们研究了紫杉醇在血管内皮细胞系 ECV304 黏附和迁移中的作用。因此，研究了 ECV304 细胞分离和再附着过程中血管扩张刺激磷蛋白（VASP）磷酸化和环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）活性的变化。结果表明，紫杉醇（10 μg/l）存在时，VASP 磷酸化的减少与 PKA 活性的抑制平行。进行细胞黏附实验和二维及三维细胞迁移实验，以确定紫杉醇对 ECV304 细胞黏附和迁移的影响。紫杉醇显著抑制 ECV304 细胞的黏附（p<0.05）和迁移（p<0.05）。这些数据表明，紫杉醇的抑制作用可能是通过抑制 PKA 活性降低 VASP 的磷酸化，从而在 ECV304 细胞黏附和迁移过程中产生的。
