Intimal hyperplasia recurs after removal of PDGF-AB and -BB inhibition in the rat carotid artery injury model
Intimal hyperplasia recurs after removal of PDGF-AB and -BB inhibition in the rat carotid artery injury model
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DOI：
10.1161/01.atv.20.11.e89
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发表时间：
2000-11-01
影响因子：
8.7
通讯作者：
Heldin, CH
中科院分区：
文献类型：
--
作者：
Leppänen, O;Janjic, N;Heldin, CH
最近开发了几种针对血小板衍生生长因子（PDGF）或其受体的特异性拮抗剂，并在各种动物模型中显示出可抑制内膜增生的形成，但研究这种干预措施持久性的数据有限。本研究旨在研究 PDGF B 链适体（一种新型 PDGF-AB 和 -BB 拮抗剂）在大鼠颈动脉模型中的效力，并表征对病变形成的中期影响。一百三十四只动物被随机分配接受适配体治疗或安慰剂。每日使用拮抗剂治疗可使病灶大小在 2 周时减少 50%（P < 0.001）。有益的作用包括增加细胞凋亡，并可能干扰平滑肌细胞迁移。与磷酸盐缓冲盐水处理的对照组相比，提前 1 周停止给药并没有带来任何显着的益处。当给予拮抗剂2周并在6周后对血管进行分析时，有益效果消失，并且与2周终点研究中治疗的病变相比，治疗的病变具有更高的内膜中膜和面积细胞比率。我们的研究结果证实了 PDGF B 链在内膜增生中的作用，但成功使用 PDGF 拮抗剂可能需要长期治疗或与其他药物联合治疗。
Several antagonists specific for platelet-derived growth factor (PDGF) or its receptors have recently been developed and shown to inhibit intimal hyperplasia formation in various animal models, but data investigating the durability of this intervention is limited. The present study was designed to investigate the potency of PDGF B-chain aptamer, a novel type of PDGF-AB and -BB antagonist, in the rat carotid model and to characterize intermediate-term effects on lesion formation. One hundred thirty-four animals were randomized to aptamer treatment or placebo. Daily treatment with the antagonist resulted in a 50% reduction in lesion size at 2 weeks (P < 0.001). The beneficial effect involved increased apoptosis and possibly an interference with smooth muscle cell migration. Discontinuing administration 1 week earlier did not give any significant benefit compared with phosphate-buffered saline-treated controls. When the antagonist was administered for 2 weeks and the vessels analyzed 6 weeks later, the beneficial effect was lost and the treated lesions had a higher intima-media and area-cell ratio compared with the treated lesions in the 2-week-endpoint study. Our findings confirm a role of PDGF B-chain in intimal hyperplasia, but the successful use of PDGF antagonists may require either prolonged treatment or combination therapy with other agents.