Ho H C, Hsu S L, Ting C T, Kuo C Y, Yang V C
Department of Life Science, Tunghai University, Taichung, Taiwan, ROC.
Cell Mol Biol (Noisy-le-grand). 2009 Nov 15;55 Suppl:OL1161-7.
Over the last two decades, significant advances have been made in percutaneous coronary intervention (PCI) for the treatment of atherosclerotic plaques. However, restenosis after PCI still challenges both vascular biologists and interventional cardiologists. In this study, we found that caffeic acid phenethyl ester (CAPE) displayed an inhibitory effect on human coronary smooth muscle cell (HCSMC) growth and migration. Flow cytometry analysis showed that the ratio of S phase increased after exposing cells to CAPE for 48-72 h. Pretreatment of cells with CAPE significantly suppressed Cyclin E, CDK2, Cyclin A, and proliferating-cell nuclear antibody expression. We demonstrated that CAPE inhibited AKT 1 and MEK1/2 activation. Using a local infusion system, CAPE was able to regress the intima thickening of the iliac artery in rabbits after balloon injury. The percentage of intimal thickening decreased significantly to 55.0 +/- 0.12 in the group after local CAPE infusion compared to the group after saline infusion (98.3 +/- 0.41%). In conclusion, CAPE can inhibit the proliferation and migration of HCSMCs by inducing cell cycle arrest. Decreased cell cycle genes and associated signaling pathway target gene expression may mediate anti-proliferative and anti-migration effects of CAPE. Furthermore, CAPE prevents intima thickening in rabbits after balloon angioplasty. These results indicate that CAPE may have therapeutic relevance for the prevention of restenosis during PCI in the treatment of coronary artery diseases.
在过去二十年中，经皮冠状动脉介入治疗（PCI）在治疗动脉粥样硬化斑块方面取得了重大进展。然而，PCI后的再狭窄仍然是血管生物学家和介入心脏病学家面临的挑战。在本研究中，我们发现咖啡酸苯乙酯（CAPE）对人冠状动脉平滑肌细胞（HCSMC）的生长和迁移具有抑制作用。流式细胞术分析表明，将细胞暴露于CAPE 48 - 72小时后，S期比例增加。用CAPE预处理细胞可显著抑制细胞周期蛋白E、细胞周期蛋白依赖性激酶2（CDK2）、细胞周期蛋白A和增殖细胞核抗体的表达。我们证明CAPE抑制AKT 1和MEK1/2的激活。使用局部输注系统，CAPE能够使兔球囊损伤后髂动脉内膜增厚消退。与生理盐水输注组相比，局部CAPE输注组内膜增厚百分比显著降低至55.0±0.12，而生理盐水输注组为98.3±0.41%。总之，CAPE可通过诱导细胞周期停滞来抑制HCSMC的增殖和迁移。细胞周期基因及相关信号通路靶基因表达的降低可能介导了CAPE的抗增殖和抗迁移作用。此外，CAPE可预防兔球囊血管成形术后内膜增厚。这些结果表明，CAPE在冠状动脉疾病治疗的PCI过程中预防再狭窄可能具有治疗意义。
