Effect of percutaneous adenovirus-mediated Gax gene delivery to the arterial wall in double-injured atheromatous stented rabbit iliac arteries

Maillard, Luc; Belle, Éric Van; Tio, Fermin O.; Rivard, Alain; Kearney, Marianne; Branellec, Didier; Steg, Ph. Gabriel; Isner, Jeffrey M.; Walsh, Kenneth

doi:10.1038/sj.gt.3301255

Cited by 42 publications

(25 citation statements)

References 69 publications

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“…Overexpression of cell cycle inhibitors, such as p21 and p27 by an adenoviral technology or p53 by a naked plasmid vector, significantly reduced neointimal hyperplasia in several animal models (168)(169)(170)(171)(172). In addition, increased expression of the homeobox gene GAX reduced the vasculoproliferative response after arterial wall injury in both rat and rabbit models (173)(174)(175). As well, overexpression of nitric oxide synthase gene has reduced neointimal proliferation in an animal model (51).…”

Section: Gene Therapy Approachmentioning

confidence: 95%

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

Charron

Nili

Strauss

2006

Canadian Journal of Cardiology

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Section: Gene Therapy Approachmentioning

confidence: 95%

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

Charron

Nili

Strauss

2006

Canadian Journal of Cardiology

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“…Adenoviral gax over-expression in a more complex model of vascular injury in the rabbit inhibited neointimal hyperplasia and lumen loss. This model closely mimics clinical angioplasty procedures since the rabbits used were fed on a high cholesterol diet such that stented arteries became atheromatous (Maillard et al 2000).…”

Section: Targeting Negative Regulators Of the Cell Cyclementioning

confidence: 99%

Targeting the cell cycle machinery for the treatment of cardiovascular disease

Bicknell

Surry

Brooks

2003

Journal of Pharmacy and Pharmacology

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Cardiovascular disease represents a major clinical problem affecting a significant proportion of the world's population and remains the main cause of death in the UK. The majority of therapies currently available for the treatment of cardiovascular disease do not cure the problem but merely treat the symptoms. Furthermore, many cardioactive drugs have serious side effects and have narrow therapeutic windows that can limit their usefulness in the clinic. Thus, the development of more selective and highly effective therapeutic strategies that could cure specific cardiovascular diseases would be of enormous benefit both to the patient and to those countries where healthcare systems are responsible for an increasing number of patients. In this review, we discuss the evidence that suggests that targeting the cell cycle machinery in cardiovascular cells provides a novel strategy for the treatment of certain cardiovascular diseases. Those cell cycle molecules that are important for regulating terminal differentiation of cardiac myocytes and whether they can be targeted to reinitiate cell division and myocardial repair will be discussed as will the molecules that control vascular smooth muscle cell (VSMC) and endothelial cell proliferation in disorders such as atherosclerosis and restenosis. The main approaches currently used to target the cell cycle machinery in cardiovascular disease have employed gene therapy techniques. We will overview the different methods and routes of gene delivery to the cardiovascular system and describe possible future drug therapies for these disorders. Although the majority of the published data comes from animal studies, there are several instances where potential therapies have moved into the clinical setting with promising results.

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“…This was recently shown in a peripheral rabbit stent-injury model with the use of adenoviral Gax transfer. 44 Many promising pharmacological treatments in small-animal models have subsequently proven ineffective in patients. Our experimental stent-injury model differs significantly from diseased, lipid-rich atherosclerotic arteries in patients.…”

Section: Vermeersch Et Al L-arginine and In-stent Stenosismentioning

confidence: 99%

l -Arginine Administration Reduces Neointima Formation After Stent Injury in Rats by a Nitric Oxide-Mediated Mechanism

Vermeersch

Zhang

Stabile

et al. 2001

ATVB

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Abstract-The clinical outcome of vascular stenting is limited by in-stent stenosis. Increased nitric oxide (NO)/cGMP signaling by L-arginine (L-Arg) supplementation, the substrate for NO synthase (NOS), or NOS gene transfer may reduce in-stent neointima formation. After stenting, vascular cell proliferation in rat carotid arteries, as measured by 5Ј-bromodeoxyuridine (5Ј-BrdU) incorporation, indicated 15Ϯ8%, 28Ϯ5%, and 33Ϯ7% 5Ј-BrdU-positive vascular cells at 4, 7, and 14 days, respectively. Reporter ␤-galactosidase gene transfer efficacy was evidenced by 30% ␤-galactosidase-expressing medial smooth muscle cells at 14 days. The intima-to-media ratio (I/M) progressively increased to 2.32Ϯ0.24 at 14 days. To target in-stent neointima formation, animals were infected with adenoviral vectors (4ϫ10 10 plaque-forming units per mL) expressing NOS2 (AdNOS2) or no transgene (AdRR5), or they received daily doses of L-Arg (500 mg · kg Ϫ1 · dϪ1 IP). The neointima at 14 days was smaller in L-Arg-treated than in untreated rats (I/M 1.25Ϯ0.35 vs 2.32Ϯ0.24, PϽ0.05, nϭ7 each) or in AdRR5-and AdNOS2-infected rats (I/M 2.57Ϯ0.43, nϭ7 and 1.82Ϯ0.75, nϭ8, respectively; PϽ0.05 for both). The effect of L-Arg was abolished by simultaneous administration of N G -nitro L-arginine methyl ester, an NOS inhibitor (2.03Ϯ0.39, PϽ0.05, vs L-Arg). Inflammation was markedly less in L-Arg-and AdNOS2-treated than in AdRR5-infected rats. Supplemental L-Arg reduces neointima formation after stenting by way of an NOS-dependent mechanism and may be a valuable strategy to target in-stent stenosis. Key Words: arginine Ⅲ neointima formation Ⅲ gene therapy Ⅲ stents Ⅲ nitric oxide synthase T he most significant drawback of angioplasty and stenting remains in-stent stenosis with luminal narrowing, characterized by a fibroproliferative response and by increased matrix production. 1 Pharmacological interventions have proven ineffective in reducing in-stent stenosis in patients, spurring interest in alternative treatment strategies, including brachytherapy and intracoronary gene transfer. Brachytherapy, based on the principle that proliferating cells are more sensitive to ionizing radiation, has shown favorable results in initial clinical trials, 2 but long-term efficacy and safety remain a concern. 3 In contrast, molecular approaches with transfer of the cytotoxic thymidine kinase, 4 retinoblastoma, 5 nitric oxide synthase (NOS), 6 -9 and tumor suppressor 10,11 genes have shown benefit in reducing neointima formation in rodent and porcine balloon-injured peripheral arteries. Most gene-based strategies have been tested in the carotid artery balloon denudation model. However, in the majority of percutaneous interventions in patients, stent deployment is used, indicating the need for experimental stent-injury models to evaluate new therapies for restenosis.Strategies aimed at increasing local NO concentrations in the injured vessel wall by NOS transfer or by administration of L-arginine (L-Arg) reduced intimal hyperplasia in experimental balloon-injury models [1...

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Effect of percutaneous adenovirus-mediated Gax gene delivery to the arterial wall in double-injured atheromatous stented rabbit iliac arteries

Cited by 42 publications

References 69 publications

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

Targeting the cell cycle machinery for the treatment of cardiovascular disease

l -Arginine Administration Reduces Neointima Formation After Stent Injury in Rats by a Nitric Oxide-Mediated Mechanism

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