Vascular endothelial growth factor increases microvascular permeability via a Ca(2+)-dependent pathway

Bates, DO; Curry, F. E.

doi:10.1152/ajpheart.1997.273.2.h687

Cited by 112 publications

(126 citation statements)

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“…VEGF is a relatively endothelial cell-specific mitogen, promoting endothelial cell growth and survival (Alon et al, 1995;Ferrara and Davis-Smyth, 1997;Gerber et al, 1998aGerber et al, , 1998b. VEGF also causes increased vessel permeability and induction of a fenestrated phenotype, two features of VEGF bioactivity that are responsible for the increased leakiness and retinal hemorrhages seen in severe ROP (Roberts and Palade, 1995;Bates and Curry, 1997).…”

Section: Vegf and Abnormal Retinal Vascularizationmentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

618

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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Section: Vegf and Abnormal Retinal Vascularizationmentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

618

527

View full text Add to dashboard Cite

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“…27 Vascular endothelial growth factor causes vasodilation through dose-dependent nitric oxide release from endothelial cells. 28 By increasing hydraulic conductivity, 29 inducing fenestrations across cell bodies, 30 and dissolving the tight junctions between endothelial cells by activating matrix metalloproteinases and phosphorylating both vascular endothelial cell cytoskeletal proteins 31 and the junctional proteins occludin and ZO-1, 32 VEGF breaks down the blood-retinal barrier, thereby increasing capillary leakage into the intercellular matrix. By modulating the phosphatidylinositol 3-kinase/Akt pathway, VEGF acts as a…”

Section: Vegf Synthesis and Physiologymentioning

confidence: 99%

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Stewart

2012

Mayo Clinic Proceedings

166

105

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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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“…9 It has been shown that VEGF also induces an increase in hydraulic conductivity of isolated microvessels and that such an effect is mediated by increased calcium influx. 10 Other studies have suggested that another important role of VEGF in the regulation of microvasclar permeability is the induction of a fenestrated phenotype in at least certain endothelial cell. 11 VEGF induces the expression of the serine proteases urokinase-and tissue-type plasminogen activators (PAs) and also PA inhibitor 1 (PAI-1) in cultured bovine microvasuclar endothelial cells.…”

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confidence: 99%