In-Stent Restenosis

Kawai, Kenji; Virmani, Renu; Finn, Aloke V.

doi:10.1016/j.iccl.2022.02.005

Cited by 10 publications

(7 citation statements)

References 105 publications

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“…While the delivery of antiproliferative agents from vascular stents has reduced the incidence of restenosis in coronary artery disease patients with non-complex lesions [ 23 ], the long-term safety of DES remains compromised by delayed healing, hypersensitivity, and local inflammation, all contributing to neointimal hyperplasia and neoatherosclerosis [ 24 ]. As a result, the long-term risk of in-stent restenosis remains significant even with the newest DES devices available today [ 2 ].…”

Section: Resultsmentioning

confidence: 99%

Nanocarrier Design for Dual-Targeted Therapy of In-Stent Restenosis

Alferiev,

Zhang,

Folchman-Wagner

et al. 2024

Pharmaceutics

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The injury-triggered reocclusion (restenosis) of arteries treated with angioplasty to relieve atherosclerotic obstruction remains a challenge due to limitations of existing therapies. A combination of magnetic guidance and affinity-mediated arterial binding can pave the way to a new approach for treating restenosis by enabling efficient site-specific localization of therapeutic agents formulated in magnetizable nanoparticles (MNPs) and by maintaining their presence at the site of arterial injury throughout the vulnerability period of the disease. In these studies, we investigated a dual-targeted antirestenotic strategy using drug-loaded biodegradable MNPs, surface-modified with a fibrin-avid peptide to provide affinity for the injured arterial wall. The MNPs were characterized with regard to their magnetic properties, efficiency of surface functionalization, disassembly kinetics, and interaction with fibrin-coated substrates. The antiproliferative effects of MNPs formulated with paclitaxel were studied in vitro using a fetal cell line (A10) exhibiting the defining characteristics of neointimal smooth muscle cells. Animal studies examined the efficiency of combined (physical/affinity) MNP targeting to stented arteries in Sprague Dawley rats using fluorimetric analysis and fluorescent in vivo imaging. The antirestenotic effect of the dual-targeted therapy was determined in a rat model of in-stent restenosis 28 days post-treatment. The results showed that MNPs can be efficiently functionalized to exhibit a strong binding affinity using a simple two-step chemical process, without adversely affecting their size distribution, magnetic properties, or antiproliferative potency. Dual-targeted delivery strongly enhanced the localization and retention of MNPs in stented carotid arteries up to 7 days post-treatment, while minimizing redistribution of the carrier particles to peripheral tissues. Of the two targeting elements, the effect of magnetic guidance was shown to dominate arterial localization (p = 0.004 vs. 0.084 for magnetic targeting and peptide modification, respectively), consistent with the magnetically driven MNP accumulation step defining the extent of the ultimate affinity-mediated arterial binding and subsequent retention of the carrier particles. The enhanced arterial uptake and sustained presence of paclitaxel-loaded MNPs at the site of stent deployment were associated with a strong inhibition of restenosis in the rat carotid stenting model, with both the neointima-to-media ratio (N/M) and % stenosis markedly reduced in the dual-targeted treatment group (1.62 ± 0.2 and 21 ± 3 vs. 2.17 ± 0.40 and 29 ± 6 in the control animals; p < 0.05). We conclude that the dual-targeted delivery of antirestenotic agents formulated in fibrin-avid MNPs can provide a new platform for the safe and effective treatment of in-stent restenosis.

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Section: Resultsmentioning

confidence: 99%

Nanocarrier Design for Dual-Targeted Therapy of In-Stent Restenosis

Alferiev,

Zhang,

Folchman-Wagner

et al. 2024

Pharmaceutics

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“…Self-expanding stents may have a long stenosis span and insufficient pressure release, resulting in poor apposition of the stent to the vessel wall and increasing the risk of postoperative stent migration. [ 4 , 5 ] One self-expanding stent does not completely cover the stenotic segment, and several stents still need to be implanted in a stitched fashion. Therefore, drug-eluting stents were chosen to be implanted into the stenotic segment of the left internal carotid artery for the long-term benefit of the patient.…”

Section: Discussionmentioning

confidence: 99%

Splice implantation of multiple drug-eluting stents for tandem severe stenosis of the internal carotid artery: A case report

Dai,

Shu,

Zhu

et al. 2024

Medicine

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Rationale: Severe stenosis of the internal carotid artery tandem affects the blood supply to the brain and threatens human life, which can be solved by interventional procedures. Patient concerns: A 64-year-old male patient presented with a sudden onset of dizziness, palpitation, numbness, and weakness of the limbs. Imaging studies suggested multiple tandem severe stenoses from the left internal carotid artery contrast C2 to C4. Diagnosis: Severe stenosis of the left internal carotid tandem. Interventions: Multiple drug-eluting stent splicing and implantation were performed. Outcomes: The left internal carotid artery stenosis was released, intracranial vascular filling was significantly improved, and the patient recovered well. Lessons: Interventional implantation of multiple drug-eluting stents relieves tandem severe stenosis of the internal carotid artery, with a wide range of applicability, high safety profile, and rapid postoperative recovery compared with endothelial debridement procedures.

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“…ISR is the common complication during the development of cardiovascular stents, which means that the luminal area lost more than 50% examined by coronary angiography. 54 Besides the inadequate expansion of stents, neointima hyperplasia (NH) and neoatherosclerosis (NA) are the two main reasons for ISR. 55 Scheme 1 Illustration of the endothelial dysfunction on implanted stent and the corresponding measures to restore endothelial function.…”

Section: Anti-stenosis Propertiesmentioning

confidence: 99%