Pires Nuno M M, Jukema J Wouter, Daemen Mat J A P, Quax Paul H A
TNO-Quality of Life, Gaubius Laboratory, Zernikedreef 9, 2333 CK Leiden, The Netherlands.
Vascul Pharmacol. 2006 May;44(5):257-64. doi: 10.1016/j.vph.2006.01.011. Epub 2006 Mar 9.
In 2001, the first human study with drug-eluting stents (DES) was published showing a nearly complete abolition of restenosis by using a sirolimus-eluting stent. This success was very encouraging to test new compounds in combination with the DES platform. Nevertheless, several other anti-restenotic compounds have been used in human clinical trials with disappointing outcomes. Little is known concerning potential adverse effects on vessel wall integrity and (re)healing, atherosclerotic lesion formation, progression, and plaque stability of these DES. Although efficacy and safety need to be determined clinically, preclinical testing of candidate drugs in well-defined animal models is extremely helpful to gain insight into the basic biological responses to candidate compounds. Here, we discuss and report an animal model which enables rapid screening of candidate drugs for DES on an atherosclerotic background. The results from drug testing using this novel model could help to quickly and cost-effectively establish the dose range of candidate drugs with reasonable potential for DES.
2001年,首项关于药物洗脱支架(DES)的人体研究发表,该研究表明使用西罗莫司洗脱支架可几乎完全消除再狭窄。这一成功极大地鼓舞了人们在DES平台上测试新化合物。然而,其他几种抗再狭窄化合物在人体临床试验中的结果却令人失望。关于这些DES对血管壁完整性和(再)愈合、动脉粥样硬化病变形成、进展及斑块稳定性的潜在不良影响,人们了解甚少。尽管疗效和安全性需要通过临床确定,但在明确的动物模型中对候选药物进行临床前测试,对于深入了解对候选化合物的基本生物学反应极为有帮助。在此,我们讨论并报告一种动物模型,该模型能够在动脉粥样硬化背景下快速筛选用于DES的候选药物。使用这种新型模型进行药物测试的结果,有助于快速且经济高效地确定具有合理DES潜力的候选药物的剂量范围。