Vascular endothelial growth factor-induced angiogenic gene therapy in patients with peripheral artery disease

Kim, Hyun‐Joong; Jang, Shin Yi; Park, Joong-Il; Byun, Jun Soo; Kim, Dong Ik; Do, Yongtae; Kim, Jong-Mook; Kim, Sun‐Young; Kim, Byong-Moon; Kim, Won-Bae; Kim, Duk Kyung

doi:10.1038/emm.2004.44

Cited by 88 publications

(63 citation statements)

References 26 publications

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“…One of the significant obstacles to successful pancreatic islet transplantation is inadequate graft vascularization during the first few days after implantation, as this may result in the dysfunction and death of the transplanted islet tissue. An angiogenic growth factor, VEGF (vascular endothelial growth factor) has been widely used in vascular diseases, ischemic injuries, and in other transplanted areas (Byun et al, 2001;Kim et al, 2004;Lee et al, 2004, Melo et al, 2004. Moreover, VEGF gene therapy was reported to increase islet graft revascularization in a mouse model .…”

Section: Introductionmentioning

confidence: 99%

Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice

Chae

Lee²,

Oh³

et al. 2005

Exp Mol Med

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Hypoxic damage is one of the major causes of islet graft failure and VEGF is known to play a crucial role in revascularization. To address the effectiveness of a cationic lipid reagent as a VEGF gene carrier, and the beneficial effect of VEGF-transfected islets on glycemic control, we used effectene lipid reagent in a transfection experiment using mouse islets. Transfection efficiencies were highest for 4 µg/µL cDNA and 25 µL effectene and cell viabilities were also satisfactory under this condition, and the overproduction of VEGF mRNA and protein were confirmed from conditioned cells. A minimal number of VEGF-transfected islets (100 IEQ/animal) were transplanted into streptozotocin (STZ)-induced diabetic mice. Hyperglycemia was not controlled in the islet transplantation (IT)-alone group (0/8) (nondiabetic glucose mice number/total recipient mice number) or in the IT-pJDK control vector group (0/8). However, hyperglycemia was completely abrogated in the IT-pJDK-VEGF transduced group (8/8), and viable islets and increased VEGF-transfected grafts vascularization were observed in renal capsules. These studies support the usefulness of VEGFtransfected islet delivery using a cationic lipid reagent to achieve euglycemia using a minimal number of islets.

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Section: Introductionmentioning

confidence: 99%

Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice

Chae

Lee²,

Oh³

et al. 2005

Exp Mol Med

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“…The purpose of this study was to establish a safe and effective gene therapeutic angiogenesis using the seldom-investigated AAV-mediated angiogenin (ANG1) gene transfer system, rAAV-ANG1 (Kastrup, 2003;Rissanen et al, 2003;Kim et al, 2004;Lee et al, 2005). We selected ANG1 as a potential therapeutic gene and AAV as a safer and effective gene delivery vector because of the following characteristics.…”

Section: Discussionmentioning

confidence: 99%

“…Since 1994, when the VEGF was first applied as a treatment for patients with peripheral vascular disease, VEGF and FGF have been most commonly applied to develop angiogenic gene therapy using various delivery vehicles. These studies showed positive effects for the promotion of neo-vascularisation (Kastrup, 2003;Rissanen et al, 2003;Kim et al, 2004;Lee et al, 2005). However, VEGF has mostly been either associated with stimulated angiogenesis in tumors, production of nonfunctional leaky vessels or used for enhancement of atherosclerotic plaque development through an increase in focal macrophage levels.…”

Section: Introductionmentioning

confidence: 99%

A novel way of therapeutic angiogenesis using an adeno-associated virus-mediated angiogenin gene transfer

Cho¹,

Park²,

Cho³

et al. 2007

Exp Mol Med

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To develop a novel therapeutic angiogenesis for the treatment of cardiovascular diseases, angiogenin (ANG1) was examined as a potential therapeutic gene. An adeno-associated virus (AAV)-mediated gene delivery system was used to measure the therapeutic efficacy of ANG1. Using a triple cotransfection technique, rAAV-ANG1-GFP, rAAV-VEGF-GFP and rAAV-GFP vectors were produced, which were then used to infect human umbilical vein endothelial cells (HUVECs) in order to evaluate in vitro angiogenic activities. Their protein expressions, tagged with green fluorescent protein (GFP), were monitored by confocal microscopy. The functional activities were measured using woundhealing HUVEC migration assays. The number of migrated cells stimulated by both the expressed ANG1 and the VEGF in rAAV-infected HUVECs increased almost twice the number observed in the expressed GFP control. In vivo angiogenic activities of the expressed ANG1 or VEGF were determined using mouse angiogenesis assays. The angiogenic activities of ANG1 or VEGF expressed in the injected mice were increased by 1.36 and 2.16 times, respectively, compared to those of the expressed GFP control. These results demonstrate that the expressed ANG1 derived from rAAV infection has in vitro and in vivo angiogenic activities and suggest that the rAAV-ANG1 vector is a potential strategy for therapeutic angiogenesis.

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“…For example, VEGF has been tumorigenic [225,226], and FGF has been associated with proliferative membranous nephropathy in mouse models [227][228][229]. Also, the induction of hypotension after delivery of these growth factors is a concern because VEGF can cause systemic hypotension and edema of the lower extremity clinically [230,231] and FGF plays an essential role in the prevention of hypertension [232]. Most of these concerns have not been reported in clinical trials to date.…”

Section: Ih In Av Fistulasmentioning

confidence: 99%

Cardiovascular gene delivery: The good road is awaiting☆

Brewster

Brey

Greisler

2006

Advanced Drug Delivery Reviews

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Atherosclerotic cardiovascular disease is a leading cause of death worldwide. Despite recent improvements in medical, operative, and endovascular treatments, the number of interventions performed annually continues to increase. Unfortunately, the durability of these interventions is limited acutely by thrombotic complications and later by myointimal hyperplasia followed by progression of atherosclerotic disease over time. Despite improving medical management of patients with atherosclerotic disease, these complications appear to be persisting. Cardiovascular gene therapy has the potential to make significant clinical inroads to limit these complications. This article will review the technical aspects of cardiovascular gene therapy; its application for promoting a functional endothelium, smooth muscle cell growth inhibition, therapeutic angiogenesis, tissue engineered vascular conduits, and discuss the current status of various applicable clinical trials.

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Vascular endothelial growth factor-induced angiogenic gene therapy in patients with peripheral artery disease

Cited by 88 publications

References 26 publications

Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice

Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice

A novel way of therapeutic angiogenesis using an adeno-associated virus-mediated angiogenin gene transfer

Cardiovascular gene delivery: The good road is awaiting☆

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