Modulation of vascular remodeling induced by a brief intraluminal exposure to the recombinant R7020 strain of Herpes simplex-1

Baldwin, Zachary K.; Chandiwal, Amito; Balasubramanian, Viji; Pearce, Benjamin J.; Curi, Michael A.; Skelly, Christopher L.; Huang, Wei; Vosicky, James; Roizman, Bernard; Weichselbaum, Ralph R.; Schwartz, Lewis B.

doi:10.1016/j.jvs.2004.10.026

Cited by 2 publications

(2 citation statements)

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“…Once in the wall, R7020 preferentially infects vascular SMCs and inhibits cellular proliferation, and will do so in immune-competent hosts [ 17 , 20 ]. The inhibition of IH by R7020 has been shown to be sustainable in experimental models of vein graft and angioplasty failure [ 18 , 21 ]. In addition, R7020 treated vessels will re-endothelialize which is critical for vein graft health and function [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Use of Multiple Mechanisms by Herpes Simplex Virus-1 R7020 to Inhibit Intimal Hyperplasia

McCormick

Stern

et al. 2015

PLoS ONE

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Intimal hyperplasia (IH) is the primary cause of vein bypass graft failure. The smooth muscle cell (SMC) is a key element of IH as it phenotypically switches from a contractile to a synthetic state which can become pathological. R7020, which is an engineered strain of Herpes Simplex Virus-1, inhibits IH in animal models. Although it has many characteristics which make it a strong candidate for use as a prophylactic agent how it inhibits IH is not well understood. The objective of this study was to identify modes of action used by R7020 to function in blood vessels that may also contribute to its inhibition of IH. The cytopathic effect of R7020 on SMCs was determined in vitro and in a rabbit IH model. In vitro assays with R7020 infected SMCs were used to quantify the effect of dose on the release kinetics of the virus as well as the effects of R7020 on cell viability and the adhesion of peripheral blood mononuclear cells (PBMCs) to SMCs in the absence and presence of tumor necrosis factor alpha (TNF-α). The observed cytopathic effect, which included R7020 positive filopodia that extend from cell to cell and the formation of syncytia, suggests that R7020 remains cell associated after egress and spreads cell to cell instead of by diffusion through the extracellular fluid. This would allow the virus to rapidly infect vascular cells while evading the immune system. The directionality of the filopodia in vivo suggests that the virus preferentially travels from the media towards the intima targeting SMCs that would lead to IH. The formation of syncytia would inhibit SMC proliferation as incorporated cells are not able to multiply. It was also observed that R7020 induced the fusion of PBMCs with syncytia suggesting the virus may limit the effect of macrophages on IH. Furthermore, R7020 inhibited the proliferative effect of TNF-α, an inflammatory cytokine associated with increased IH. Thus, the results of this study suggest that R7020 inhibits IH through multiple mechanisms.

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Section: Introductionmentioning

confidence: 99%

Evidence for the Use of Multiple Mechanisms by Herpes Simplex Virus-1 R7020 to Inhibit Intimal Hyperplasia

McCormick

Stern

et al. 2015

PLoS ONE

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“…On the other hand, investigators have also used intraluminal delivery of both viral and nonviral vectors in canine [8][9][10] and rabbit 11,12 models of vein grafts. In these reports, gene transfer was performed ex vivo after vein harvest.…”

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confidence: 99%

Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium

Hashimoto

Yamamoto

Foster

et al. 2016

JoVE

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Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The simple murine AVF model was combined with intraluminal administration of drug solution to the venous endothelium at the same time as fistula creation. Technical aspects of this model are discussed. Under general anesthesia, an abdominal incision is made and the aorta and inferior vena cava (IVC) are exposed. The infra-renal aorta and IVC are dissected for clamping. After proximal and distal clamping, the puncture site is exposed and a 25 G needle is used to puncture both walls of the aorta and into the IVC. Immediately after the puncture, a reporter gene-expressing viral vector was infused in the IVC via the same needle, followed by 15 min of incubation. The intraluminal administration method enabled more robust viral gene delivery to the venous endothelium compared to administration by the external route. This novel method of delivery will facilitate studies that explore the role of the endothelium in AVF maturation and enable intraluminal drug delivery at the time of surgical operation.

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Modulation of vascular remodeling induced by a brief intraluminal exposure to the recombinant R7020 strain of Herpes simplex-1

Abstract: A brief exposure of the neurovirulence-attenuated HSV-1 strain R7020 results in an increased ratio of luminal radius to wall thickness in experimental vein grafts chronically exposed to low shear stress.

Cited by 2 publications

References 43 publications

Evidence for the Use of Multiple Mechanisms by Herpes Simplex Virus-1 R7020 to Inhibit Intimal Hyperplasia

Evidence for the Use of Multiple Mechanisms by Herpes Simplex Virus-1 R7020 to Inhibit Intimal Hyperplasia

Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium

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