Efficient inhibition of in-stent restenosis by controlled stent-based inhibition of elastase: A pilot study
Efficient inhibition of in-stent restenosis by controlled stent-based inhibition of elastase: A pilot study
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DOI：
10.1097/01.rvi.0000141340.67588.4f
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发表时间：
2004-11-01
影响因子：
2.9
通讯作者：
Dake, MD
中科院分区：
文献类型：
--
作者：
Ganaha, F;Ohashi, K;Dake, MD
目的：提出局部弹性蛋白酶抑制可以抑制细胞外基质（ECM）降解和随后的平滑肌细胞迁移，并限制随后的支架内再狭窄。本研究在兔支架模型中评估了基于支架的可控弹性蛋白酶抑制对支架植入术后再狭窄的影响。材料与方法：制备含有强效弹性酶抑制剂a-l-抗胰蛋白酶（AAT）的可生物降解微球。体外证实微球每日释放AAT。微球被装入一个腔内聚合物储层的支架中。将AAT微球和空白微球（对照组）分别植入兔腹主动脉，每组6只。支架置入后，所有支架均过度扩张至125%直径。7天后（每个n = 3）或28天后（每个n = 3）采集支架植入动脉。为了评估AAT局部递送的效果，我们分析了支架植入主动脉的弹性蛋白酶活性和弹性蛋白含量。作为终点，在7天和28天的标本中测定内膜与中膜（I/M）比率。结果：在支架植入后7天，实验组血管中弹性蛋白酶的抑制作用明显高于对照组（P < 0.05）。弹性蛋白酶活性的降低足以提供支架内新生内膜的早期和晚期减少。与对照组相比，弹性酶抑制组28天内斑块进展减少67% （P < 0.05）。结论：基于支架的弹性蛋白酶抑制剂控释可显著降低ECM降解，并可能限制支架内再狭窄。
PURPOSE: It is proposed that local elastase inhibition could suppress the extracellular matrix (ECM) degradation and subsequent smooth muscle cell migration and limit subsequent in-stent restenosis. This study evaluated the effect of stent-based controlled elastase inhibition on restenosis after stent implantation in a rabbit model.MATERIALS AND METHODS: Biodegradable microspheres containing the potent elastase inhibitor a-l-antitrypsin (AAT) were prepared. Daily release of AAT from the microspheres was confirmed in vitro. The microspheres were loaded into stents with an abluminal polymer reservoir. Implantation of the stent with AAT microspheres and blank microspheres (control) was performed in the abdominal aortae of six rabbits in each group. After stent deployment, all stents were overdilated to 125% diameter. Stent-implanted arteries were harvested after 7 days (n = 3 each) or 28 days (n = 3 each). To assess the effect of local delivery of AAT, elastase activity and elastin content of the stent-implanted aortae were analyzed. As an endpoint, intima-to-media (I/M) ratio was determined in the 7-day and 28-day specimens.RESULTS: Significant inhibition of elastase was confirmed in treated vessels versus controls at 7 days after stent implantation (P < .05). This reduction in elastase activity was sufficient to afford early and late reduction of in-stent neointima. Plaque progression in the 28-day specimens decreased to 67% with elastase inhibition relative to controls (P < .05).CONCLUSION: Stent-based controlled release of elastase inhibitor may significantly reduce ECM degradation and might limit in-stent restenosis.