Catheter-based prostacyclin synthase gene transfer prevents in-stent restenosis in rabbit atheromatous arteries

Numaguchi, Yasushi; Okumura, Kenji; Harada, Mitsunori; Naruse, Keiji; Yamada, Masahito; Osanai, Hiroyuki; Ito, Masafumi; Murohara, Toyoaki

doi:10.1016/j.cardiores.2003.10.016

Cited by 27 publications

(29 citation statements)

References 38 publications

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“…40 The proliferation index of glomeruli of Tg rabbits was compared with that of control rabbits at 40 wk. BrdU (50 mg/kg) was subcutaneously injected at 1,8,16, and 24 h before the removal of the kidney.…”

Section: Proliferation Index In Glomerulusmentioning

confidence: 99%

Increased Expression of Vascular Endothelial Growth Factor in Kidney Leads to Progressive Impairment of Glomerular Functions

Liu

Morimoto

Kitajima

et al. 2007

Journal of the American Society of Nephrology

105

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Vascular endothelial growth factor (VEGF) is an important mediator in maintaining normal kidney functions. In addition, several lines of evidence suggest that upregulation of VEGF in glomeruli may be associated with or cause renal dysfunction such as diabetic nephropathy. For elucidation of the pathologic consequences of high levels of VEGF in glomeruli, transgenic (Tg) rabbits that express human VEGF 165 isoform in both kidney and liver under the control of the human ␣-1-antitrypsin promoter were generated and characterized. With the use of heterozygous Tg rabbits and their littermates aged 8 to 55 wk, renal functions and structures were investigated. Compared with control rabbits, Tg rabbits exhibited progressive proteinuria with increased GFR at the early stage and decreased GFR at the later stage. Histologic examinations revealed that Tg rabbit kidneys were characterized by considerable glomerular hypertrophy as a result of increased proliferation of both glomerular capillaries and mesangial cells accompanied by prominent podocyte hypertrophy. With increasing age starting from 20 wk, Tg rabbit kidneys showed prominent formation of microaneurysms and capillary proliferation at the vascular pole area. At a later stage (55 wk), many glomeruli showed sclerosis and tuft collapse with the formation of glomerular cysts on a background of tubular atrophy and interstitial fibrosis. This study provides the first evidence that increased expression of VEGF in glomeruli directly causes the glomerular hypertrophy that is associated with proteinuria, suggesting that VEGF exerts multiple effects on the glomerular pathophysiologic processes.

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Section: Proliferation Index In Glomerulusmentioning

confidence: 99%

Increased Expression of Vascular Endothelial Growth Factor in Kidney Leads to Progressive Impairment of Glomerular Functions

Liu

Morimoto

Kitajima

et al. 2007

Journal of the American Society of Nephrology

105

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“…Индуцированная экспрессия VEGF приводи-ла к росту и восстановлению эндотелия сосудов после повреждения. Также было показано, что по-вышение экспрессии гена простациклин-синтазы ускоряет реэндотелиализацию и предотвращает образования неоинтимы в травмированных баллоном артериях в предклинической модели [56]. Тем не менее этот эффект был замечен в со-четании с доставкой гена VEGF и вполне может быть связан с более поздней трансдукцией гена.…”

Section: гены стимулирующие реэндотелиализациюunclassified

Achievements and Prospects in the Field of Gene-Eluting Coronary Stents

Фаттахов¹,

Куликов²,

Литвинова³

2016

Kompleks. probl. serdečno-sosud. zabol.

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1 Федеральное государственное автономное образовательное учреждение высшего образования «Балтийский федеральный университет имени Иммануила Канта». Калининград, Россия 2 Федеральное государственное бюджетное образовательное учреждение высшего образования «Северо-Западный государственный медицинский университет им. И. И. Мечникова». Санкт-Петербург, Россия В настоящем обзоре систематизированы основные современные разработки и достижения в области ген-выделяющих стен-тов; обсуждены их преимущества и недостатки как потенциальной альтернативы непокрытым металлическим стентам и стентам, выделяющим лекарства. Рассмотрены основные стратегии оптимизации, необходимые для перевода основанных на применении ген-выделяющих стентов технологий из экспериментальной сферы в клиническую медицину.Ключевые слова: ген-выделяющий стент, ген, рестеноз, вектор, ишемическая болезнь сердца, чрескожное коронарное вме-шательство. In this paper, we summarize the main recent developments and achievements in the field of gene-eluting stents, their advantages and disadvantages as a potential alternative to the bare metal stents and drug-eluting stents are discussed. the basic optimization strategies required for the translation of technologies based on the use of gene-eluting stents from experimental sphere to clinical medicine are examined. ACHIEVEMENTS AND PROSPECTS IN THE FIELD OF GENE-ELUTING CORONARY STENTS

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“…Gene transfer of PGI 2 synthase has also been shown to accelerate re-endothelialization and prevent neointimal formation in balloon-injured arteries. In a rabbit model, PGI 2 synthase gene delivery by the lipotransfection method via dispatch catheter can accelerate re-endothelialization and attenuate neointimal formation (36). Douglas et al (20) found that endothelial-specific overexpression of GTP-cyclohydrolase-1 can enhance endothelial cell function and increases NO production, thus promoting re-endothelialization after stent deployment.…”

Section: Evolution Of Antirestenosis Therapymentioning

confidence: 99%

“…Takemoto et al (60) found that transfection of the human pE-NTPDase gene, encoding an enzyme that rapidly hydrolyzes ATP and ADP to AMP via cationic gelatin-coated stents, inhibits subacute in-stent thrombosis and suppresses neointimal hyperplasia and inflammation without antiplatelet drugs. More established antithrombotic genes, including PGI 2 synthase, COX-1 and tissue factor pathway inhibitor, have been investigated in recent years for their potential in postangioplasty intervention, and have demonstrated successful suppression of thrombosis and/or restenosis in various animal models (34,36,58,61).…”

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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Catheter-based prostacyclin synthase gene transfer prevents in-stent restenosis in rabbit atheromatous arteries

Abstract: PGIS gene transfer accelerated re-endothelialization, and attenuated neointimal formation after stent implantation in atheromatous rabbit arteries, at least in part, via increased production of VEGF protein.

Cited by 27 publications

References 38 publications

Increased Expression of Vascular Endothelial Growth Factor in Kidney Leads to Progressive Impairment of Glomerular Functions

Increased Expression of Vascular Endothelial Growth Factor in Kidney Leads to Progressive Impairment of Glomerular Functions

Achievements and Prospects in the Field of Gene-Eluting Coronary Stents

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

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