A Paclitaxel-Eluting Stent for the Prevention of Coronary Restenosis

Park, Seung Jung; Shim, Won Heum; Ho, David Sai Wah; Raizner, Albert E.; Park, Seong Wook; Hong, Myeong Ki; Lee, Cheol Whan; Choi, Donghoon; Jang, Yangsoo; Lam, R.K.; Weissman, Neil J.; Mintz, Gary S.

doi:10.1056/nejmoa021007

Cited by 397 publications

(131 citation statements)

References 27 publications

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“…However, the major limitation of PCI is related to restenosis, which occurs in 20–40% of patients within the first 6 months [1]. Stent, and especially drug-eluting stent (DES), implantations substantially reduce the angiographic restenosis rate [2, 3]. On the other hand, even with DES, restenosis remains a problem in some patients and lesion subgroups, e.g., diabetics or bifurcation stenosis.…”

Section: Introductionmentioning

confidence: 99%

Local Delivery of 17-Beta-Estradiol Modulates Collagen Content in Coronary Porcine Arteries after PTCA and Stent Implantation

et al. 2008

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Background: Percutaneous transluminal coronary angioplasty (PTCA) and stent implantation are associated with intimal hyperplasia and extracellular matrix (ECM) accumulation, resulting in restenosis. We showed that local delivery of 17-beta-estradiol (17βE) reduced restenosis following PTCA and stent implantation by 47 and 23%, respectively. Because estrogens decreased type I and type III collagen synthesis in vitro, we hypothesized that local delivery of 17βE may influence intimal hyperplasia formation by modulating ECM expression. Methods: Porcine coronary arteries underwent PTCA or stenting and were randomly assigned to 17βE or placebo. After 28 days, animals were sacrificed for histology and collagen type I and III content analysis. Results: Both collagen subtypes increased in the media by 1.7 to 2.6-fold after PTCA and by 15.7 to 16.1-fold after stenting, as compared to PTCA segments. In the neointima, the ratio of collagen type III to type I was 2.7 in stented arteries and only 0.3 in PTCA arteries. In the neointima of 17βE-treated animals, collagen type I (but not type III) content upregulation was limited by 53% after PTCA and by 74% after stenting. Conclusion: Local delivery of 17βE reduces restenosis, in part by decreasing the density of collagen type I in the neointima in PTCA and stented arteries.

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Section: Introductionmentioning

confidence: 99%

Local Delivery of 17-Beta-Estradiol Modulates Collagen Content in Coronary Porcine Arteries after PTCA and Stent Implantation

et al. 2008

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“…Studies on the prevention of in-stent restenosis (ISR) remain a central issue in interventional cardiology. Currently, drug-eluting stents are the principal approach for avoiding ISR [4, 5]. For the further development of next-generation drug-eluting stents, a high throughput model for the screening of stents and gaining insight into pathophysiological mechanisms of ISR is essential.…”

Section: Introductionmentioning

confidence: 99%

Rat Abdominal Aorta Stenting: A New and Reliable Small Animal Model for In-Stent Restenosis

Langeveld¹,

Roks²,

Tio³

et al. 2004

J Vasc Res

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Background: A high throughput animal model may enhance pathophysiological studies to mechanisms of in-stent restenosis (ISR). More and appropriate antibodies and transgenic and knockout strains are available in rats. Consequently, a model for ISR in the rat would be convenient for pathobiological studies. Here we present the full characteristics of a rat ISR model suitable for high throughput stent research. Methods: The abdominal aorta of rats was separated from surrounding tissue and a BeStent™ 2 or a Cypher™ sirolimus-eluting stent was locally inserted. After 1, 3, 7, 28 and 56 days, the aortas were harvested, fixed, embedded and cut. Morphometric analysis was performed and inflammation scored. Results: The neointimal area increased to a maximum after 28 days (0.55 ± 0.08 mm²). Subsequently, the neointimal area slightly decreased. The injury score and the neointimal area were linearly correlated (r = 0.85, p < 0.01). Thrombus formation was present after 1 day. Leukocyte adherence was evident after 1 day, maximal after 3 days (93 ± 21 cells/section) and decreased thereafter. The inflammation score increased after 3 days to a maximum after 7 days (1.37 ± 0.06) and declined thereafter. After 28 days the Cypher sirolimus-eluting stent decreased the stenosis in comparison to the BeStent 2 (10.2 ± 0.85 vs. 18.0 ± 2.0%, respectively, p < 0.01). Conclusions: Stent deployment in the rat abdominal aorta results in thrombus formation, inflammation and neointimal formation. Moreover, there is a linear correlation between the injury score and the neointimal area. These responses resemble ISR events as seen in other animal models. Moreover, a known anti-restenotic stent also reduces neointimal formation in this model. Rat abdominal aorta stenting is a promising animal model for ISR, it is suitable for testing commercially manufactured stents and studying the pathophysiology of ISR.

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“…Restenosis following percutaneous transluminal angioplasty has emerged as a complex multifactorial pathophysiological problem that has to be addressed by a combined mechanical and pharmacological approach [3,25,26,27]. Animal models showing decreased neointimal thickening [4, 5] provided the basis for controlled clinical trials with sirolimus- or paclitaxel-eluting stents [6, 7,41,42,43]. However, the reduction in restenosis events achieved by such stents is associated with a higher incidence of late stent thrombosis [8,9,10,11,12,13].…”

Section: Discussionmentioning

confidence: 99%

Gliotoxin Inhibits Neointimal Hyperplasia after Vascular Injury in Rats

et al. 2008

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Neointima formation participates in the pathophysiology of atherosclerosis and restenosis. Proliferation and migration of vascular smooth muscle cells (VSMC) are initial responses to vascular injury. The aim of the present study was to assess the effect of gliotoxin, an inhibitor of nuclear factor (NF)-κB, on migration and proliferation of cultured rat VSMC and neointimal formation in injured rat vessels. In cultured VSMC, gliotoxin inhibited the nuclear translocation of the p65 subunit of NF-κB in response to inflammatory stimuli. In addition, gliotoxin inhibited VSMC migration and proliferation in response to platelet-derived growth factor-BB. This was associated with a rapid rearrangement of the F-actin and vimentin cytoskeleton. Furthermore, gliotoxin inhibited endothelial cell nuclear translocation of p65, cell surface expression of adhesion molecules such as VCAM-1, ICAM-1 and E-selectin, and monocytic cell adhesion to a cytokine-activated endothelial monolayer. In the rat carotid artery balloon catheter injury model, the systemic administration of gliotoxin for 10 days decreased neointimal hyperplasia and luminal stenosis by up to 90% and decreased the expression of proliferating cell nuclear antigen in the vessel wall by up to 70%, depending on the dose. These observations suggest that gliotoxin favorably regulates the response to vascular injury through actions on VSMC. However, further studies evaluating the therapeutic benefit of gliotoxin in restenosis after balloon angioplasty are required.

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A Paclitaxel-Eluting Stent for the Prevention of Coronary Restenosis

Abstract: Paclitaxel-eluting stents used with conventional antiplatelet therapy effectively inhibit restenosis and neointimal hyperplasia, with a safety profile similar to that of standard stents.

Cited by 397 publications

References 27 publications

Local Delivery of 17-Beta-Estradiol Modulates Collagen Content in Coronary Porcine Arteries after PTCA and Stent Implantation

Local Delivery of 17-Beta-Estradiol Modulates Collagen Content in Coronary Porcine Arteries after PTCA and Stent Implantation

Rat Abdominal Aorta Stenting: A New and Reliable Small Animal Model for In-Stent Restenosis

Gliotoxin Inhibits Neointimal Hyperplasia after Vascular Injury in Rats

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