Therapeutic Angiogenesis: Protein and Gene Therapy Delivery Strategies

Rosengart, Todd K.; Patel, Shailen R.; Crystal, Ronald G.

doi:10.1177/204748739900600106

Cited by 45 publications

(24 citation statements)

References 149 publications

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“…Preliminary results utilizing this approach as the sole therapy for patients with chronic myocardial ischemia suggest that direct injection of VEGF as naked DNA into cardiac myocytes may improve collateral blood flow and reduce the frequency of, and threshold for, myocardial ischemia (Losordo et al, 1998;Symes et al, 1999). Therapeutic angiogenesis is an innovative approach to the treatment of ischemic diseases, whereby the administration of the VEGF gene facilitates the "biological revascularization" of obstructed vascular segments, and the reperfusion of ischemic tissues (Rosengart et al, 1999). Moreover, it has been suggested that in certain cases of heart failure, the angiographically occult intramural coronary vasculature consists the locus of the disease as well as the cure .…”

Section: Discussionmentioning

confidence: 99%

“…Angiogenic gene therapy to promote the development of supplemental collateral blood vessels in chronic myocardial ischemia has been exploited using direct myocardial administration of the vascular endothelial growth factor (VEGF) gene, in the form of naked DNA (Rosengart et al, 1999). Preliminary results using this strategy suggest that it may constitute an alternative treatment for patients with severe myocardial ischemia (Losordo et al, 1998;Symes et al, 1999) and heart failure (Carmeliet et al, 1999;Isner et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA

Jeong

Byun²,

Jeon³

et al. 2002

Exp Mol Med

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Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid DNA into the myocardium was shown to induce development of new blood vessels to increase the circulation in the heart of patients with coronary artery diseases. However, such angiogenic gene therapy (via naked DNA) was limited by low level of gene expression. Furthermore, the temporal and spatial characteristics of VEGF gene transfer in the heart are not known. In this study, we demonstrated that a plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE) promoter and enhancer, induces greater expression of gene in the rat heart monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter, than four different viral and cellular promoters. Interestingly, expression of VEGF 121 protein showed an earlier peak, a shorter duration, and a wider distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE promoter/enhancer provides clear advantages over other previously developed plasmids. Furthermore, expression profile of VEGF 121 gene may provide useful information in the design of angiogenic gene therapy in the heart.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA

Jeong

Byun²,

Jeon³

et al. 2002

Exp Mol Med

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“…Furthermore, these therapies are not options for a significant number of individuals in whom the extent of vascular pathology is especially severe or widespread. Angiogenesis, the growth of new vasculature, is a critical biological response to ischemia that provides collateralization, or ''biological revascularization'' of vascular obstructions [45]. Evidence exists to support the concept that a graft lined with a significant number of endothelial cells (EC) would consequently lead better graft survival [46] LELI has been demonstrated to positively influence cellular proliferation for the process of angiogenesis on EC [2,47].…”

Section: Discussionmentioning

confidence: 99%

Low‐energy laser irradiation increases endothelial cell proliferation, migration, and eNOS gene expression possibly via PI3K signal pathway

2008

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Background and Objectives: The purpose of this study, therefore, was to determine the mechanisms by which lowenergy laser irradiation (LELI) may exert some of its angiogenic effects via the PI3 kinase/eNOS signaling pathway and induce endothelial cell migration and neovascularization, an important and necessary part of wound healing. Study Design/Materials and Methods: The possible molecular mechanism of helium-neon (He-Ne) laser irradiation on endothelial cells was proposed. He-Ne laser at 632.5 nm was used to stimulate human umbilical vein endothelial cell (HUVEC), and its effect on cell proliferation, nitric oxide secretion, and cell migration was determined. Results: Irradiation enhanced endothelial nitric oxidase synthase (eNOS) protein expression, and irradiation of less than 0.26 J/cm 2 enhanced eNOS gene expression in HUVEC. The cell migration ability was promoted for HUVEC irradiated with 0.26 J/cm 2 . This agreed with the vinculin protein expression induced by irradiation. In addition, the angiogenesis was promoted. The induced eNOS expression was inhibited by LY294002, indicating that the effect of laser on EC could be attributed to the upregulation of eNOS expression through PI3K pathway at the cellular and molecular levels as a result of the He-Ne laser. Conclusions: The study has shown that LELI increased endothelial cell proliferation, migration, NO secretion, and identified that activation of PI3K/Akt pathway was a critical step for the elevated for eNOS expression upon LELI.

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“…1,2 This approach is based on the knowledge that in the adult heart, the genes coding for angiogens and their receptors are expressed in low levels, apparently insufficient in most individuals to provide robust formation of collaterals in response to chronic ischemia. 3,4 Vascular endothelial growth factor (VEGF), a protein coded by a 7-exon gene localized on chromosome 6, serves as a major angiogen in normal cardiac development.…”

mentioning

confidence: 99%

Angiogenesis Gene Therapy

Rosengart

Lee²,

Patel³

et al. 1999

Circulation

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583

131

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Background —Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1 − E3 − adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad GV VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. Methods and Results —Ad GV VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. Conclusions —The data are consistent with the concept that direct myocardial administration of Ad GV VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

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Therapeutic Angiogenesis: Protein and Gene Therapy Delivery Strategies

Cited by 45 publications

References 149 publications

Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA

Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA

Low‐energy laser irradiation increases endothelial cell proliferation, migration, and eNOS gene expression possibly via PI3K signal pathway

Angiogenesis Gene Therapy

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