Basic fibroblast growth factor is released from endothelial extracellular matrix in a biologically active form

Presta, Marco; Maier, Jeanette A.M.; Rusnati, Marco; Ragnotti, Giovanni

doi:10.1002/jcp.1041400109

Cited by 132 publications

(61 citation statements)

References 21 publications

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“…Bovine aortic endothelial cells (BAE cells) (passage 4-10) were a gift from Dr. El Sabban (Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York). Transformed FBAE GM 7373 cells (15) were obtained from the National Institute of General Medical Sciences Human Genetic Mutant Cell Repository (Camden, NJ). Both cell types were maintained in Eagle's minimal essential medium (MEM) containing 10% fetal bovine serum (FBS), essential and nonessential amino acids and antibiotics.…”

Section: Methodsmentioning

confidence: 99%

BCL-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells.

Giardino¹,

Edelstein²,

Brownlee³

1996

J. Clin. Invest.

223

121

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Hyperglycemia rapidly induces an increase in intracellular advanced glycation end products (AGEs) in bovine endothelial cells, causing an alteration in bFGF activity (Giardino, I., D. Edelstein, and M. Brownlee. 1994. J. Clin. Invest. 94:110-117). Because sugar or sugar-adduct autoxidation is critical for AGE formation in vitro, we evaluated the role of reactive oxygen species (ROS) in intracellular AGE formation, using bovine aortic endothelial cells. 30 mM glucose increased intracellular ROS formation by 250% and lipid peroxidation by 330%, while not affecting ROS in the media. In cells depleted of glutathione, intracellular AGE accumulation increased linearly with ROS generation as measured by immunoblotting and the fluorescent probe DCFH (AGE 0.258-3.531 AU* mm ր 5 ϫ 10 4 cells, DCF 57-149 mean AU, r ϭ .998, P Ͻ .002). Deferoxamine, ␣ -tocopherol, and dimethylsulfoxide each inhibited hyperglycemia-induced formation of both ROS and AGE. To differentiate an effect of ROS generation on AGE formation from an effect of more distal oxidative processes, GM7373 endothelial cell lines were generated that stably expressed the peroxidationsuppressing proto-oncogene bcl-2. bcl-2 had no effect on hyperglycemia-induced intracellular ROS formation. In contrast, bcl-2 expression decreased both lipid peroxidation (100% at 3 h and 29% at 168 h) and AGE formation (55% at 168 h). These data show that a ROS-dependent process plays a central role in the generation of intracellular AGEs, and that inhibition of oxidant pathways prevents intracellular AGE formation. (

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Section: Methodsmentioning

confidence: 99%

BCL-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells.

Giardino¹,

Edelstein²,

Brownlee³

1996

J. Clin. Invest.

223

121

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“…On the contrary, cellassociated HSPGs can directly activate a signal transduction pathway in response to FGF2 [124], promote FGF2 internalization [125,126], and are required for a correct presentation of FGFs to FGFRs, leading to the formation of productive HSPGs/FGF/FGFR ternary complexes [121]. Finally, HSPGs of the ECM act as a reservoir for FGF2 that reaches higher local concentrations and sustains the long- term stimulation of endothelial cells [127]. A schematic representation of the effects exerted by the heparin/HSPGs system on the biology of FGFs is shown in Fig.…”

Section: Heparin and Hspgsmentioning

confidence: 99%

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Presta

Dell’Era

Mitola

et al. 2005

Cytokine & Growth Factor Reviews

1,129

870

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Fibroblast growth factors (FGFs) are a family of heparin-binding growth factors. FGFs exert their pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. Their activity is modulated by a variety of free and extracellular matrix-associated molecules. Also, the cross-talk among FGFs, vascular endothelial growth factors (VEGFs), and inflammatory cytokines/chemokines may play a role in the modulation of blood vessel growth in different pathological conditions, including cancer. Indeed, several experimental evidences point to a role for FGFs in tumor growth and angiogenesis. This review will focus on the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization. #

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“…bFGF is stored at high concentration within the extracellular matrix (ECM) as an inactive complex, and released when endothelial cells dissolve ECM via the release of proteases. [221][222][223] bFGF and hypoxia act synergistically to not only induce mitogenesis in endothelial cells, but also to upregulate VEGF in smooth muscle cells and endothelial cells, resulting in retinal angiogenesis. 224 However, the fact that bFGF-deficient animal models develop the same degree of retinal neovascularization as wild-type animals argues against a major angiogenic role for bFGF in diabetic retinopathy.…”

Section: Igf-imentioning

confidence: 99%

The pathogenesis of diabetic retinopathy: old concepts and new questions

Cai

Boulton

2002

Eye

294

196

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Hyperglycaemia appears to be a critical factor in the aetiology of diabetic retinopathy and initiates downstream events including: basement membrane thickening, pericyte drop out and retinal capillary non-perfusion. More recently, focus has been directed to the molecular basis of the disease process in diabetic retinopathy. Of particular importance in the development and progression of diabetic retinopathy is the role of growth factors (eg vascular endothelial growth factor, placenta growth factor and pigment epithelium-derived factor) together with specific receptors and obligate components of the signal transduction pathway needed to support them. Despite these advances there are still a number of important questions that remain to be answered before we can confidently target pathological signals. How does hyperglycaemia regulate retinal vessels? Which growth factors are most important and at what stage of retinopathy do they operate? What is the preferred point in the growth factor signalling cascade for therapeutic intervention? Answers to these questions will provide the basis for new therapeutic interventions in a debilitating ocular condition.

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Basic fibroblast growth factor is released from endothelial extracellular matrix in a biologically active form

Cited by 132 publications

References 21 publications

BCL-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells.

BCL-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells.

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

The pathogenesis of diabetic retinopathy: old concepts and new questions

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