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Drug-eluting stents studies in mice: Do we need atherosclerosis to study restenosis?

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Author: Pires, N.M.M. · Jukema, J.W. · Daemen, M.J.A.P. · Quax, P.H.A.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:Vascular Pharmacology, 5, 44, 257-264
Identifier: 239255
doi: doi:10.1016/j.vph.2006.01.011
Keywords: Health · Biomedical Research · (Histo)Pathology · Animal models · Atherosclerosis · Drug-eluting stents · Restenosis · 7 hexanoyltaxol · Dactinomycin · Dexamethasone · Everolimus · Paclitaxel · Paclitaxel derivative · Qp 2 · Rapamycin · Tacrolimus · Thalidomide · Unclassified drug · Artery intima proliferation · Atherosclerosis · Blood pressure variability · Clinical trial · Coronary stent · Cost effectiveness analysis · Disease exacerbation · Disease model · Drug efficacy · Drug eluting stent · Drug release · Drug safety · Evaluation · Healing impairment · Hypersensitivity reaction · In-stent restenosis · Mouse strain · Nonhuman · Pain · Rash · Respiratory tract disease · Restenosis · Side effect · Thrombosis · Animals · Atherosclerosis · Coronary Restenosis · Disease Models, Animal · Drug Delivery Systems · Drug Evaluation, Preclinical · Humans · Mice · Paclitaxel · Sirolimus · Stents

Abstract

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. © 2006 Elsevier Inc. All rights reserved. Chemicals / CAS: dactinomycin, 1402-38-6, 1402-58-0, 50-76-0; dexamethasone, 50-02-2; everolimus, 159351-69-6; paclitaxel, 33069-62-4; rapamycin, 53123-88-9; tacrolimus, 104987-11-3; thalidomide, 50-35-1; Paclitaxel, 33069-62-4; Sirolimus, 53123-88-9