The VIVA Trial

Henry, Timothy D.; Annex, Brian H.; McKendall, George R.; Azrin, Michael; López, John J.; Giordano, Frank J.; Shah, PK; Willerson, James T.; Benza, Raymond L.; Berman, Daniel S.; Gibson, C. Michael; Bajamonde, Alex; Rundle, Amy Chen; Fine, Jennifer; McCluskey, Edward R.

doi:10.1161/01.cir.0000061911.47710.8a

Cited by 919 publications

(315 citation statements)

References 23 publications

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“…In the present study, we demonstrated that cell therapy using hMSCs was superior to VEGF and Ang1 gene therapy in enhancing angiogenesis and improving cardiac function after myocardial infarction in mice. The clinical results reported from two recent clinical angiogenesis trials [19,20] suggest that strategies involving administration of a single angiogenic agent may not result in optimal angiogenesis. Stem cells express and secrete Ang1, VEGF, and other cytokines [21,22], which are important contributors for angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

Shyu

Wang²,

Hung³

et al. 2005

J Biomed Sci

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SummaryBoth cell therapy and angiogenic growth factor gene therapy have been applied to animal studies and clinical trials. Little is known about the direct comparison between cell therapy and angiogenic growth factor gene therapy. The goal of this study was to compare the effects of human bone marrow-derived mesenchymal stem cells (hMSCs) transplantation and injection of angiogenic growth factor genes in a model of acute myocardial infarction in mice. The hMSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of hMSCs were identified by flow cytometry and immunophenotyping. Immediately after ligation of the left anterior descending coronary artery in male severe combined immunodeficient (SCID) mice, culture-expanded hMSCs or angiogenic growth factor genes were injected intramuscularly at the left anterior free wall. The engrafted hMSCs were positive for cardiac marker, desmin. Infarct size was significantly smaller in the hMSCs-treated group than in the angiopoietin-1 (Ang-1) or vascular endothelial growth factor (VEGF)-treated group at day 28 after infarction. hMSCs transplantation was better in decreasing left ventricular end-diastolic dimension and increasing fractional shortening than Ang1 or VEGF gene therapy. Capillary density was markedly increased after hMSCs transplantation than Ang1 and VEGF gene therapy. In conclusion, intramyocardial transplantation of hMSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium. hMSCs are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction. Transplantation of MSCs may become the future therapy for acute myocardial infarction for myocardial regeneration.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

Shyu

Wang²,

Hung³

et al. 2005

J Biomed Sci

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“…1 Recent elaboration of mechanisms regulating angiogenesis has led to extensive efforts to identify and exploit potential agents stimulating angiogenesis under circumstances when the recruitment of new blood vessels is desired, for instance in coronary heart disease or peripheral arterial disease. [2][3][4][5][6][7] Conversely, the need for inhibitors of angiogenesis directed against angiogenesis in pathophysiological conditions such as tumor growth or proliferative diabetic retinopathy has arisen. 8 Among angiogenic growth factors, ligands for receptor tyrosine kinases (RTKs) such as vascular endothelial growth factor (VEGF) have been identified to play an essential role in vascular development.…”

Section: Introductionmentioning

confidence: 99%

Discordant effects of a soluble VEGF receptor on wound healing and angiogenesis

et al. 2004

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Soluble receptors to vascular endothelial growth factor (VEGF) can inhibit its angiogenic effect. Since angiogenesis is involved in wound repair, we hypothesized that adenovirus-mediated gene transfer of a soluble form of VEGF receptor 2 (Flk-1) would attenuate wound healing in mice. C57Bl/6J and genetically diabetic (db/db) mice (each n¼20) received intravenous (i.v.) injections of recombinant adenoviruses (10 9 PFU) encoding the ligand-binding ectodomain of VEGF receptor 2 (Flk-1) or cDNA encoding the murine IgG2a Fc fragment (each n¼10). At 4 days after gene transfer, two full-thickness skin wounds (0.8 cm) were created on the dorsum of each animal. Wound closure was measured over 9-14 days after which wounds were resected for histological analysis. Prior to killing, fluorescent microspheres were systemically injected for quantitation of wound vascularity. Single i.v. injections of adenoviruses encoding soluble Flk-1 significantly decreased wound angiogenesis in both wild-type and diabetic mice. Fluorescence microscopy revealed a 2.0-fold (wild type) and 2.9-fold (diabetic) reduction in wound vascularity in Flk-1-treated animals (po0.05). Impairment of angiogenesis was confirmed by CD31 immunohistochemistry. Interestingly, despite significant reductions in wound vascularity, wound closure was not grossly delayed. Our data indicates that while VEGF function is essential for optimal wound angiogenesis, it is not required for wound closure.

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“…10 In adults, VEGF infusion stimulates microvascular perfusion in patients with severe coronary artery disease and ischemic limbs. 11,12 Although new blood vessel growth in response to ischemic myocardium may be lifesaving, 13 pathologic neovascularization and hyperpermeability in other organs, such as the eye, cause blindness from retinal detachment, uncontrollable glaucoma, and untreatable retinal edema.…”

mentioning

confidence: 99%

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Stewart

2012

Mayo Clinic Proceedings

160

103

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Vascular endothelial growth factor (VEGF) plays an important role in both physiologic and pathologic angiogenesis and contributes to increased permeability across both the blood-retinal and blood-brain barriers. After 2 decades of extensive research into the VEGF families and receptors, specific molecules have been targeted for drug development, and several medications have received US Food and Drug Administration approval. Bevacizumab, a full-length antibody against VEGF approved for the intravenous treatment of advanced carcinomas, has been used extensively in ophthalmology for exudative age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, retinopathy of prematurity, and other chorioretinal vascular disorders. Pegaptanib and ranibizumab have been developed specifically for intraocular use, whereas the soon-to-be-introduced aflibercept (VEGF Trap-Eye) is moving through clinical trials for both intraocular and systemic use. Although these drugs exhibit excellent safety profiles, ocular and systemic complications, particularly thromboembolic events, remain a concern in patients receiving therapy. Patients experiencing adverse events that may be related to VEGF suppression should be carefully evaluated by both the ophthalmologist and the medical physician to reassess the need for intraocular therapy and explore the feasibility of changing medications. For this review a search of PubMed from January 1, 1985 through April 15, 2011, was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, diabetic retinopathy, retina vein occlusions, retinopathy of prematurity, intravitreal injections, bevacizumab, ranibizumab, and VEGF Trap. Studies were limited to those published in English. Other articles were identified from bibliographies of retrieved articles and archives of the author.

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The VIVA Trial

Cited by 919 publications

References 23 publications

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

Discordant effects of a soluble VEGF receptor on wound healing and angiogenesis

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

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