Fibroblast Growth Factor 2 Activation of Stromal Cell Vascular Endothelial Growth Factor Expression and Angiogenesis

Claffey, Kevin P.; Abrams, Kristin; Shih, Shu-Ching; Brown, Lawrence F.; Mullen, Andrew R.; Keough, Martin P.

doi:10.1038/labinvest.3780212

Cited by 92 publications

(50 citation statements)

References 67 publications

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“…This model provides a useful tool in mice for investigating the effect of a variety of angiogenic and antiangiogenic factors, as previously reported (Claffey et al, 2001;Passaniti et al, 1997). As the Matrigel plug is initially avascular, vascular-like structures located within the Matrigel plug must be newly formed, reflecting then the angiogenic process.…”

Section: Discussionmentioning

confidence: 75%

“…We also observed immunolocalization of VEGF in stromal and endothelial cells of Ang II-treated Matrigel. Similarly, FGF-2 activated VEGF expression in stromal cell and subsequent cell ingrowth within the Matrigel (Claffey et al, 2001). FGF-2 and other angiogenic stimuli have also been shown to induce VEGF expression in endothelial cells of forming capillaries (Liu et al, 1995;Seghezzi et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

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Angiotensin II Angiogenic Effect In Vivo Involves Vascular Endothelial Growth Factor- and Inflammation-Related Pathways

Tamarat

Silvestre

Durie

et al. 2002

Laboratory Investigation

207

161

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SUMMARY:Although accumulating lines of evidence indicate the proangiogenic role of angiotensin II (Ang II), little is known about the molecular mechanisms associated with such an effect. This study aimed to identify molecular events involved in Ang II-induced angiogenesis in the Matrigel model in mice. C57Bl/6 female mice received a subcutaneous injection of either Matrigel or Matrigel with Ang II (10 Ϫ7 M) alone, with Ang II and an AT1 receptor antagonist (candesartan, 10 Ϫ6 M), or with Ang II and AT2 receptor antagonist (PD123319, 10 Ϫ6 M). After 14 days, angiogenesis was assessed in the Matrigel-plug by histological evaluation and cellular counting. Ang II increased by 1.9-fold the number of cells within the Matrigel (p Ͻ 0.01 versus control). Immunohistological analysis revealed the presence of macrophages, endothelial and smooth muscle cells, and the development of vascular-like structure. Such an angiogenic effect was associated with an increase in vascular endothelial growth factor (VEGF) (1.5-fold, p Ͻ 0.01), endothelial nitric oxide (eNOS) (1.7-fold, p Ͻ 0.01), and cyclooxygenase-2 (1.4-fold, p Ͻ 0.05) protein levels measured by Western blotting. Conversely, Ang II treatment did not affect MMP-9 and MMP-2 activity, assessed by zymography. Blockade of AT1 receptor completely prevented the Ang II-induced angiogenesis and protein regulations, whereas that of AT2 was ineffective. Administration of VEGF neutralizing antibody (2.5 g ip twice a week) and cyclooxygenase-2 selective inhibitor (nimesulide, 30 mg/L) also hampered Ang II proangiogenic effect. In addition, Ang II-induced cell ingrowth was impaired by treatment with nitric oxide synthase inhibitor (L-NAME, 10 mg/kg/day) and in eNOS-deficient mice. Therefore, in an in vivo model, Ang II induced angiogenesis through AT1 receptor, which involved activation of VEGF/eNOS-related pathway and of the inflammatory process. (Lab Invest 2002, 82:747-756).

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Angiotensin II Angiogenic Effect In Vivo Involves Vascular Endothelial Growth Factor- and Inflammation-Related Pathways

Tamarat

Silvestre

Durie

et al. 2002

Laboratory Investigation

207

161

View full text Add to dashboard Cite

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“…33,34 The cellular infiltration around capillary sprouts is where immature adipocytes occur at 6 weeks and has been observed by others. 32 PDGF-BB and FGF-2 stimulate mesenchymal cell proliferation and migration, 15,29,[35][36][37] PDGF-BB stimulates preadipocyte differentiation, 30 whereas FGF-2 stimulates proliferation of adipose precursor cells. 38 Given the evidence that both factors, via several mechanisms, positively influence adipose tissue growth, it is not surprising that our study showed an increase in adipose tissue for individual applications of FGF-2 and PDGF-BB.…”

Section: Discussionmentioning

confidence: 99%

Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis

Rophael

Craft

Palmer

et al. 2007

The American Journal of Pathology

121

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De novo tissue generation stimulated by three angiogenic growth factors administered in a factorial design was studied in an in vivo murine tissue engineering chamber. A silicone chamber was implanted around the epigastric pedicle and filled with Matrigel with 100 ng/ml of recombinant mouse vascular endothelial growth factor-120 (VEGF 120 ), recombinant human basic fibroblastic growth factor (FGF-2), or recombinant rat platelet-derived growth factor-BB (PDGF-BB) added as single, double, or triple combinations. Angiogenesis, supporting tissue ingrowth, and adipogenesis were assessed at 2 and 6 weeks by immunohistochemistry and morphometry. At 2 weeks angiogenesis was synergistically enhanced by VEGF 120 ؉ FGF-2 (P ‫؍‬ 0.019). FGF-2 (P ‫؍‬ 0.008) and PDGF-BB (P ‫؍‬ 0.01) significantly increased connective tissue/inflammatory cell infiltrate (macrophages, pericytes, and preadipocytes) in double and triple combinations compared with control. At 6 weeks sequential addition of growth factors increased the percent volume of adipose tissue (P < 0.0005, each main effect), with a synergistic increase in adipose tissue in combination treatments (P < 0.0005). Groups containing 300 ng/ml of single growth factors produced significantly less adipose tissue than the triple growth factor combination (P < 0.0005, VEGF 120 and PDGF-BB; P < 0.001, FGF-2). In conclusion, angiogenic growth factor combinations increased early angiogenesis and cell infiltration resulting in synergistically increased adipose tissue growth at 6 weeks. Two way and higher level synergies are likely to be important in therapeutic applications of angiogenic growth factors.

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“…14) Both VEGF and bFGF are important growth factors for endothelial cells, but the previous findings 14) and our results indicate that the roles of these factors in angiogenesis are different; bFGF seems to be released at an early stage as a result of tissue injury, while VEGF is up-regulated in endothelial cells and mesenchymal cells in response to angiogenic stimuli such as hypoxia 28) and/or bFGF. 29) Proteolytic enzymes are another important factor in the angiogenic process. MMPs degrade the components of ECM and PA activates proteolytic enzymes, such as plasmin, which are necessary for cell migration at the early stage of angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Rat Aortic Fragment within Collagen Gel as an Angiogenesis Model; Capillary Morphology may Reflect the Action Mechanisms of Angiogenesis Inhibitors.

Hata-Sugi

Kawase-Kageyama

Wakabayashi

2002

Biological & Pharmaceutical Bulletin

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Angiogenesis, the formation of new blood vessels from pre-existing vessels, occurs physiologically during embryonal development, tissue injury and inflammation. It is also well known to play an important role in several pathological conditions, such as cancer, diabetic retinopathy, rheumatoid arthritis and atherosclerosis.1) An understanding of the angiogenic process may lead to new therapies for the above diseases, and some angiogenesis inhibitors are already under clinical study as anti-cancer drugs.2)The formation of new capillaries is a complex biological process whose regulatory mechanisms are incompletely understood. The initiation of angiogenesis involves focal reduction of intercellular interactions and of interactions between endothelial cells and the surrounding extracellular matrix (ECM). Cell migration, proliferation and capillary tube formation then follow. It is clear that complex orchestration of many processes, some overlapping, is required in order for angiogenesis to proceed. Various types of angiogenic growth factors such as vascular endothelial growth factor (VEGF), 3) basic fibroblast growth factor (bFGF), 4) platelet-derived growth factor (PDGF) 5) and hepatocyte growth factor (HGF) 6) stimulate both the endothelial cells and mesenchymal cells. ECM-degrading proteolytic enzymes, including matrix metalloprotease (MMP) and plasminogen activator (PA), are secreted by endothelial cells in response to angiogenic factors and/or cytokines. 7) Cell adhesion molecules such as integrins, cadherin and PECAM also regulate the angiogenic process.8) There are some reports on the interactions of the angiogenic factors mentioned above; for example, bFGF up-regulates VEGF production 9); the production of proteolytic enzymes and integrin alpha subunits is induced by VEGF, 10) bFGF 11) and PDGF 12); MMP-2 associates with integrin avb3 and growth factor receptor.13) Therefore, an in vitro model of angiogenesis should retain, as far as possible, the in vivo interactions of angiogenic factors and the regulatory mechanisms.Fragments of rat thoracic aorta within type I collagen gel provide a good model of the overall angiogenic process, including cell migration, proliferation and capillary tube formation, for 1 to 2 weeks. The aortic fragments contain several types of cells, such as endothelial cells, smooth muscle cells and fibroblasts, which co-ordinate to form capillary vessels in the collagen gel. It was reported that aortic fragments endogenously produce bFGF, 14) and exogenous growth factors such as PDGF, insulin-like growth fator (IGF) and VEGF enhance capillary formation. 15)In this report, we show that VEGF, its receptor and proteolytic enzymes (MMP, PA) are endogenously expressed in the rat aorta model and gradually increase during the process of angiogenesis. When the action of these endogenous factors was blocked by inhibitors, capillary tube formation was clearly inhibited, demonstrating that these endogenous factors play key roles in angiogenesis in this model. Interestingly, the formed capillaries a...

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Fibroblast Growth Factor 2 Activation of Stromal Cell Vascular Endothelial Growth Factor Expression and Angiogenesis

Cited by 92 publications

References 67 publications

Angiotensin II Angiogenic Effect In Vivo Involves Vascular Endothelial Growth Factor- and Inflammation-Related Pathways

Angiotensin II Angiogenic Effect In Vivo Involves Vascular Endothelial Growth Factor- and Inflammation-Related Pathways

Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis

Characterization of Rat Aortic Fragment within Collagen Gel as an Angiogenesis Model; Capillary Morphology may Reflect the Action Mechanisms of Angiogenesis Inhibitors.

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