VEGF-D Is the Strongest Angiogenic and Lymphangiogenic Effector Among VEGFs Delivered Into Skeletal Muscle via Adenoviruses

Rissanen, Tuomas T.; Markkanen, Johanna E.; Gruchała, Marcin; Heikura, Tommi; Puranen, Antti; Kettunen, Mikko I.; Kholová, Ivana; Kauppinen, Risto A.; Achen, Marc G.; Stacker, Steven A.; Alitalo, Kari; Ylä‐Herttuala, Seppo

doi:10.1161/01.res.0000073584.46059.e3

Cited by 383 publications

(345 citation statements)

References 39 publications

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“…In the case of VEGF-D, the affinity for VEGFR-2 is increased approximately 290-fold by proteolytic conversion of the full-length to the mature form (Stacker et al, 1999). Hence the mature forms of VEGF-C and VEGF-D can induce angiogenesis (Cao et al, 1998;Rissanen et al, 2003). The enzymes known to process VEGF-C or VEGF-D are the serine protease plasmin (McColl et al, 2003) and members of proprotein convertase (PC) family, namely furin, PC5 and PC7 (Siegfried et al, 2003).…”

Section: Mechanisms Of Lymphangiogenic Signallingmentioning

confidence: 99%

Targeting lymphangiogenesis to prevent tumour metastasis

2006

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Recent studies involving animal models of cancer and clinicopathological analyses of human tumours suggest that the growth of lymphatic vessels (lymphangiogenesis) in or nearby tumours is associated with the metastatic spread of cancer. The best validated molecular signalling system for tumour lymphangiogenesis involves the secreted proteins vascular endothelial growth factor-C (VEGF-C) and VEGF-D that induce growth of lymphatic vessels via activation of VEGF receptor-3 (VEGFR-3) localised on the surface of lymphatic endothelial cells. In this review, we discuss the evidence supporting a role for this signalling system in the spread of cancer and potential approaches for blocking this system to prevent tumour metastasis.

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Section: Mechanisms Of Lymphangiogenic Signallingmentioning

confidence: 99%

Targeting lymphangiogenesis to prevent tumour metastasis

2006

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“…3,6 -8 After Ն70 points had been mapped, 10 intramyocardial injections (5 to 6 mm deep, 0.2 mL each, total volume 2.0 mL, Ն5 mm apart from each other) were performed to the anterolateral wall. Human GMP-grade first-generation Ads 1 at 2 doses [2ϫ10 11 or 2ϫ10 12 viral particles (vp)] or naked plasmids (1 mg) were used. Both vector types encoded nuclear-targeted LacZ marker gene, human VEGF-A 165 , 10 or the mature form of human VEGF-D (VEGF-D ⌬N⌬C ) 9 driven by a CMV promoter.…”

Section: Noga Gene Transfermentioning

confidence: 99%

“…ing properties, whereas the effects of VEGF-D ⌬N⌬C , a soluble member of the VEGF family, 9,11 have not been documented previously in the myocardium. Furthermore, we compared the efficiency of naked plasmid with that of adenoviral vector, both used in clinical trials for therapeutic angiogenesis.…”

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confidence: 96%

Adenoviral Catheter-Mediated Intramyocardial Gene Transfer Using the Mature Form of Vascular Endothelial Growth Factor-D Induces Transmural Angiogenesis in Porcine Heart

et al. 2004

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Background— It is unclear what is the most efficient vector and growth factor for induction of therapeutic vascular growth in the heart. Furthermore, the histological nature of angiogenesis and potential side effects caused by different vascular endothelial growth factors (VEGFs) in myocardium have not been documented. Methods and Results— Adenoviruses (Ad) at 2 doses (2×10 11 and 2×10 12 viral particles) or naked plasmids (1 mg) encoding Lac Z control, VEGF-A 165 , or the mature, soluble form of VEGF-D (VEGF-D ΔNΔC ) were injected intramyocardially with the NOGA catheter system into domestic pigs. AdVEGF-D ΔNΔC gene transfer (GT) induced a dose-dependent myocardial protein production, as measured by ELISA, resulting in an efficient angiogenic effect 6 days after the injections. Also, AdVEGF-A 165 produced high gene transfer efficacy, as demonstrated with immunohistochemistry, leading to prominent angiogenesis effects. Despite the catheter-mediated approach, angiogenesis induced by both AdVEGFs was transmural, with maximal effects in the epicardium. Histologically, strongly enlarged α-smooth muscle actin–positive microvessels involving abundant cell proliferation were found in the transduced regions, whereas microvessel density did not change. Myocardial contrast echocardiography and microspheres showed marked increases in perfusion in the transduced areas. VEGF-D ΔNΔC but not matrix-bound VEGF-A 165 was detected in plasma after adenoviral GT. A modified Miles assay demonstrated myocardial edema resulting in pericardial effusion with the higher AdVEGF doses. All effects returned to baseline by 3 weeks. Naked plasmid–mediated GT did not induce detectable protein production or vascular effects. Conclusions— Like AdVEGF-A 165 , AdVEGF-D ΔNΔC GT using the NOGA system produces efficient transmural angiogenesis and increases myocardial perfusion. AdVEGF-D ΔNΔC could be useful for the induction of therapeutic vascular growth in the heart.

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“…However, more potent forms of VEGF [140] are currently being evaluated for their ability to limit IH in arteriovenous (AV) fistulas for hemodialysis patients.…”

Section: Inhibiting Smc Proliferation and Migrationmentioning

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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VEGF-D Is the Strongest Angiogenic and Lymphangiogenic Effector Among VEGFs Delivered Into Skeletal Muscle via Adenoviruses

Abstract: Abstract-Optimal angiogenic and lymphangiogenic gene therapy requires knowledge of the best growth factors for each purpose. We studied the therapeutic potential of human vascular

Cited by 383 publications

References 39 publications

Targeting lymphangiogenesis to prevent tumour metastasis

Targeting lymphangiogenesis to prevent tumour metastasis

Adenoviral Catheter-Mediated Intramyocardial Gene Transfer Using the Mature Form of Vascular Endothelial Growth Factor-D Induces Transmural Angiogenesis in Porcine Heart

Cardiovascular gene delivery: The good road is awaiting☆

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