Anti-CD34 Antibodies Immobilized on the Surface of Sirolimus-Eluting Stents Enhance Stent Endothelialization

Nakazawa, Gaku; Granada, Juan F.; Alviar, Carlos L.; Téllez, Armando; Kałuża, Greg L.; Guilhermier, Margaret Yoklavich; Parker, Sherry; Rowland, Stephen; Kolodgie, Frank D.; Leon, Martin B.; Virmani, Renu

doi:10.1016/j.jcin.2009.09.015

Cited by 143 publications

(111 citation statements)

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“…Endothelial cells play a vital role in vessel wall repair, thus modification of BMS and DES has been investigated by various researchers [4,5,6,7]. Nakazawa et al [4] emphasized that the stent must maintain sustained inhibition of smooth muscle cell proliferation whilst promoting endothelial cell coverage along the stent surface, thus the concept of re-endothelialization of 3 the stent became an essential factor to promote integration of the device with the vascular structure.…”

Section: The Year 2003 Marked the New Era Of Stents Johnson And Johnsomentioning

confidence: 99%

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Effect of low voltage AC fields on cardiovascular implants

Kothandaraman

Anson

Reynolds

2015

Materials Science and Engineering: C

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Coronary Artery Stents have been the preferred form of treatment for vascular occlusive disease, due to the minimally invasive surgical procedure, post-operative recovery time and cost, when compared to open coronary bypass surgery. The cellular response upon applying an AC electric field to type 316LM Stainless Steel stent mimics was investigated in this paper. The highest RBC adhesion was observed at voltages higher than 88mV and lower than 74mV.Their unique alignment along the lines of fracture on the stent surface at 88mV was a phenomenon caused by an increase in electrical conductivity in these regions. Being able to control RBC adhesion may have various clinical implications such as inhibition of thrombus formation, and provide a basis to analyse whether electric fields may be applied to cancer therapy as well.2

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Section: The Year 2003 Marked the New Era Of Stents Johnson And Johnsomentioning

confidence: 99%

“…The stents were fixed using glutaraldehyde solution and examined using Scanning Electron Microscopy (SEM) to evaluate cell behaviour. 4 …”

Section: The Year 2003 Marked the New Era Of Stents Johnson And Johnsomentioning

confidence: 99%

Effect of low voltage AC fields on cardiovascular implants

Kothandaraman

Anson

Reynolds

2015

Materials Science and Engineering: C

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“…In a porcine model of coronary restenosis, anti-CD34 antibody-coated sirolimus-eluting stents were associated with greater endothelialization, thus inhibiting platelet activation. However, a clear clinical benefit of stents coated with this technology has not been shown (58,59). ADP, a key agonist required to trigger platelet aggregation, has received much attention as a potential antithrombosis therapeutic target.…”

Section: Anti-inflammationmentioning

confidence: 99%

Gene therapy for in-stent restenosis: Targets and delivery system

Yin¹,

Agrawal²

2014

Curr Res Cardiol

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Despite the increased use of drug-eluting stents (DES), the incidence of in-stent restenosis (ISR) requiring target vessel revascularization remains unacceptably high (1,2). The incidence rate of ISR requiring target vessel revascularization (ie, 'DES failure') in the United States alone was conservatively estimated to be 10%, and may be more common in patients with diabetes mellitus (3). Although the pathophysiology of DES failure is complex, histopathological changes of in-stent neointima following directional atherectomy at the time of reintervention have been shown to be remarkably similar between bare-metal stents (BMS) and DES, suggesting that a process mediated by the endothelial injury, inflammation, proliferation and migration of vascular smooth muscle cells (VSMCs), and thrombosis plays the same important role in the progress of ISR of DES (4,5). In addition, antiproliferative drugs in DES, primarily aimed at preventing VSMC proliferation (which is central to the pathogenesis of ISR), also perturb endothelial recovery (6), which consequently increases the risk for subacute in-stent thrombosis and results in late stent thrombosis (ST) (7). Furthermore, polymer coatings on DES induce a distinct inflammatory reaction compared with bare metal surfaces (8). These results raise serious questions regarding the long-term durability and efficacy of DES, thereby resulting in an urgent need to develop new therapies to prevent restenosis. The present review focuses on the progress made to date in the use of gene therapy, including catheter-based gene delivery and gene-eluting stents (GES), to prevent ISR. We will also discuss the current and promising application of magnetic targeting gene delivery systems for antirestenosis therapy. Evolution of antirEstEnosis thErapyIn the past several decades, percutaneous transluminal coronary angioplasties have revolutionized the treatment of atherosclerosis-related cardiovascular disease. At the same time, tremendous efforts have also been made to reduce the incidence of restenosis after percutaneous transluminal coronary angioplasties (9). During the time in which 'plain old balloon angioplasty' was prevalent, rates of acute and chronic vessel occlusion were higher (30% to 56%), secondary to acute/chronic recoil and constrictive remodelling (10). These problems led to the development of a second revolutionary treatment, BMS, which were first implanted in 1986 (11). Although this 'bailout' scaffold significantly reduced the issue of acute and chronic recoil, its application was ultimately hampered by the risk for subacute thrombotic coronary artery occlusion and neointimal hyperplasia (12). The restenosis rates with BMS were reported to be between 16% and 44%, with higher rates of stenosis attributable to several risk factors, particularly long lesion length and small vessel calibre (1,13). Considerable progress to reduce the incidence of restenosis was made by the advent of DES, which are composed of a metallic stent, a polymer-based drug delivery platform and a pharmacolog...

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“…Similar results were also noted when anti-CD34 stents were assessed. 24 Enhanced re-endothelialization due to increased bioavailability of NO has been suggested to result in enhanced endothelial cell migration and/or mobilization of endothelial progenitor cells. 25,26 We speculate that in our study this may be because of the cell type targeted, that is, macrophages.…”

Section: Histomorphometrymentioning

confidence: 99%

Gene-eluting stents: non-viral, liposome-based gene delivery of eNOS to the blood vessel wall in vivo results in enhanced endothelialization but does not reduce restenosis in a hypercholesterolemic model

et al. 2011

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Although successful, drug-eluting stents require significant periods of dual anti-platelet therapy with a persistent risk of late stent thrombosis due to inhibition of re-endothelialization. Endothelial regeneration is desirable to protect against in-stent thrombosis. Gene-eluting stents may be an alternative allowing inhibition of neointima and regenerating endothelium. We have shown that adenoviral endothelial nitric oxide synthase (eNOS) delivery can result in significantly decreased neointimal formation and enhanced re-endothelialization. Here, we examined non-viral reporter and therapeutic gene delivery from a stent. We coated lipoplexes directly onto the surface of stents. These lipostents were then deployed in the injured external iliac artery of either normal or hypercholesterolemic New Zealand White rabbits and recovered after 28 days. Lipoplexes composed of lipofectin and a reporter lacZ gene or therapeutic eNOS gene were used. We demonstrated efficient gene delivery at 28 days post-deployment in the media (21.3 ± 7.5%) and neointima (26.8 ± 11.2%). Liposomal delivery resulted in expression in macrophages between the stent struts. This resulted in improved re-endothelialization as detected by two independent measures compared with vector and stent controls (Po0.05 for both). However, in contrast to viral delivery of eNOS, liposomal eNOS does not reduce restenosis rates. The differing cell populations targeted by lipoplexes compared with adenoviral vectors may explain their ability to enhance re-endothelialization without affecting restenosis. Liposome-mediated gene delivery can result in prolonged and localized transgene expression in the blood vessel wall in vivo. Furthermore, lipoeNOS delivery to the blood vessel wall results in accelerated re-endothelialization; however, it does not reduce neointimal formation. Gene Therapy (2012) 19, 321-328; doi:10.1038/gt.2011.92; published online 30 June 2011Keywords: endothelialization; coronary artery stents; restenosis; late stent thrombosis; liposome INTRODUCTION Drug-eluting stents (DES) are now routinely used for occlusive atherosclerotic coronary lesions to reduce the problem of restenosis. However, DES have been associated with a higher frequency of very late stenosis and re-infarction (more than 1 year) compared with bare metal stents, 1.9% versus 0.6% per year, respectively. 1,2 In addition, animal studies have shown that DES can cause local toxicity to the vessel wall in the form of medial necrosis, intimal proliferation, chronic inflammation and delayed re-endothelialization of the stents. 1-3 Thus, although DES reduce the risk of restenosis, they are associated with delayed re-endothelialization. 4,5 An optimal therapeutic approach would involve a strategy, which inhibits intimal hyperplasia while promoting re-endothelialization and suppressing stent-or vector-related inflammatory side effects.Gene-eluting stents have the potential to provide an alternative treatment strategy for the prevention of restenosis. The safety and feasibility of viral-medi...

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Anti-CD34 Antibodies Immobilized on the Surface of Sirolimus-Eluting Stents Enhance Stent Endothelialization

Abstract: Immobilization of anti-CD34 antibody on SES enhances endothelialization and may potentially be an effective therapeutic alternative to improve currently available drug-eluting stents.

Cited by 143 publications

References 22 publications

Effect of low voltage AC fields on cardiovascular implants

Effect of low voltage AC fields on cardiovascular implants

Gene therapy for in-stent restenosis: Targets and delivery system

Gene-eluting stents: non-viral, liposome-based gene delivery of eNOS to the blood vessel wall in vivo results in enhanced endothelialization but does not reduce restenosis in a hypercholesterolemic model

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