Vascular Endothelial Growth Factor Induces Expression of the Antiapoptotic Proteins Bcl-2 and A1 in Vascular Endothelial Cells

Gerber, Hans‐Peter; Dixit, Vishva M.; Ferrara, Napoleone

doi:10.1074/jbc.273.21.13313

Cited by 878 publications

(550 citation statements)

References 32 publications

Supporting

Mentioning

505

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, activation of iCaspase-9 was sufficient to induce apoptosis of endothelial cells in vivo resulting in ablation of human microvessels in immunodeficient mice. These results are consistent with previous observations that showed that factors such as VEGF promote endothelial cell survival by acting on various molecules including Bcl-2 and Akt, [2][3][4] that are known to function upstream of caspase-9 in the apoptosis pathway. 24 Most anti-angiogenic strategies currently in clinical trials are based on the delivery of antibodies or drugs that inhibit endothelial cell-specific survival signals and promote apoptosis by a default mechanism.…”

Section: Discussionsupporting

confidence: 93%

“…VEGF binding to its endothelial cellspecific receptor Flk-1/KDR, and engagement of the PI3 kinase-Akt and Bcl-2 signaling pathways, has been shown to protect endothelial cells against various apoptotic stimuli including growth factor deprivation. [2][3][4] The pro-angiogenic molecules angiopoietin-1, bFGF, and ␣ V ␤ 3 also mediate signaling cascades that result in enhanced survival of endothelial cells. [5][6][7] VEGF and the pro-angiogenic factors described above appear to function primarily at the level of newly formed vessels where they promote survival by repressing endothelial cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ablation of microvessels in vivo upon dimerization of iCaspase-9

Nör

Song

et al. 2002

Gene Ther

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Ablation of microvessels in vivo upon dimerization of iCaspase-9

Nör

Song

et al. 2002

Gene Ther

View full text Add to dashboard Cite

show abstract

“…This is consistent with data showing that VEGF induces expression of antiapoptotic proteins, such as Bcl-2 in human endothelial cells (Gerber et al, 1998b). Therefore, interference with the VEGF/VEGF-receptor systems leads to apoptotic cell death of endothelial cells resulting in regression of the tumor vasculature accompanied by tumor regression.…”

Section: Discussionsupporting

confidence: 92%

Expression of the vascular endothelial growth factor gene is inhibited by p73

2000

View full text Add to dashboard Cite

Recently, p73, a new member of the p53 family, has been cloned and mapped to chromosome 1p36, a region that is frequently deleted in a variety of human cancers. p73 can activate p53-responsive promoters and induce apoptosis when overexpressed in certain p53-de®cient tumor cells. In contrast to p53, analysis of the p73 gene in several human solid tumors did not reveal loss of p73 expression or mutations in the p73 gene. However, transcriptional silencing of the p73 gene by hypermethylation of a CpG island was observed in several leukemias and lymphomas. These lymphoid neoplasms also show increased expression of vascular endothelial growth factor (VEGF), an endothelial cell-speci®c mitogen and a key mediator of angiogenesis. To evaluate a possible relationship between p73 status and VEGF expression, we have studied the e ect of ectopically expressed p73 on the regulation of the VEGF gene. Our results demonstrate that p73 can down-regulate endogenous VEGF gene expression on mRNA and protein level. This e ect is mediated by transcriptional repression of the VEGF promoter and involves the promoter region 785 to 750 bp, containing a cluster of Sp 1 binding sites. Our results suggest a regulatory role for p73 in tumor angiogenesis. Oncogene (2000) 19, 3470 ± 3476.

show abstract

“…Mouse embryos with disruption of one allele of the VEGF gene have defective vascularization and reduced nucleated red blood cells within blood islands, as well as developmental anomalies in the forebrain and heart outflow tract (Carmeliet et al, 1996;Ferrara et al, 1996). In addition to exerting a mitogenic influence on endothelial cells, VEGF also functions as a survival factor (Alon et al, 1995;Ferrara and Davis-Smyth, 1997;Gerber et al, 1998aGerber et al, , 1998b. These survival effects appear to be developmentally regulated, as inhibition of VEGF results in apoptotic changes only in the neonatal vasculature (Gerber et al, 1999).…”

Section: Vegf and Retinal Vascular Developmentmentioning

confidence: 99%

“…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

636

527

View full text Add to dashboard Cite

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.

show abstract

Vascular Endothelial Growth Factor Induces Expression of the Antiapoptotic Proteins Bcl-2 and A1 in Vascular Endothelial Cells

Cited by 878 publications

References 32 publications

Ablation of microvessels in vivo upon dimerization of iCaspase-9

Ablation of microvessels in vivo upon dimerization of iCaspase-9

Expression of the vascular endothelial growth factor gene is inhibited by p73

Vascular endothelial growth factor in eye disease

Contact Info

Product

Resources

About