External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting
External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting
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DOI：
10.1038/nm0298-235
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发表时间：
1998-02-01
期刊：
影响因子：
82.9
通讯作者：
Angelini, GD
中科院分区：
文献类型：
--
作者：
Mehta, D;George, SJ;Angelini, GD
自体大隐静脉搭桥术是治疗缺血性心脏病的有效方法。然而，其长期临床成功是有限的(1，2)。晚期静脉移植失败是中层血管平滑肌细胞迁移、增殖和细胞外基质沉积导致的中膜和内膜增厚的结果，随后是叠加的动脉粥样硬化。这些变化直接影响移植物的血流并引发血栓形成。移植静脉壁增厚可能代表动脉血流动力学因子的适应(4-6)，这些因子已被证明通过激活包括血小板衍生生长因子(PDGF)在内的关键介质促进血管平滑肌细胞的迁移和增殖(7)。许多旨在防止这些长期变化的药理干预措施在临床评估中被证明不成功(8)。我们最近在猪隐静脉移植物模型中证实，在颈动脉间置静脉移植物的外侧应用外部聚酯支架可以减少植入后1个月的内膜增生和总壁厚度[9]。然而，目前尚不清楚支架的益处是否会长期保持，也不知道其效果背后的机制。因此，本研究比较了同种猪移植后6个月有支架移植物和对侧无支架移植物的形态变化和PDGF的表达。外支架移植物的中膜增厚减少、新生内膜形成和细胞增殖持续，这些效应与PDGF表达显著减少有关。
Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited(1,2). Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferation and extracellular matrix deposition, followed later by superimposed atherosclerosis(3). These changes directly compromise graft blood flow and provoke thrombosis. Vein graft wall thickening may represent an adaptation imposed by arterial hemodynamic factors(4-6), and these factors have been shown to promote vascular smooth muscle cell migration and proliferation through activation of key mediators including platelet-derived growth factor (PDGF)(7). Many pharmacological interventions aimed at preventing these long-term changes have proven unsuccessful in clinical evaluation(8). We recently demonstrated in a pig saphenous vein graft model that application of an external polyester stent to the outside of carotid interposition vein grafts reduced intimal hyperplasia and total wall thickness 1 month after implantation(9). However, it is not known whether the benefits of the stent are maintained in the longer term or what mechanisms underlie its effect. The present study therefore compared morphological changes and PDGF expression in stented grafts and contralateral unstented grafts in the same pigs, 6 months after graft implantation. Reduced medial thickening, neointima formation, and cell proliferation were sustained in externally stented grafts, and these effects were associated with a significant reduction in PDGF expression.