Vascular Endothelial Growth Factor (VEGF165) and Its Influence on Angiogenesis Versus Arteriogenesis in Different Vascular Beds

SummaryIntegrins αvβ3 and αvβ5 have been long considered as proangiogenic receptors, yet genetic ablation studies demonstrated enhanced angiogenesis in mice lacking αvβ3 and αvβ5 integrins, which was attributed to increased expression of vascular endothelial growth factor receptor-2 (VEGFR-2). In this study, we determined the effect of αvβ3 and αvβ5 suppression in endothelial cells (EC) on vascular endothelial growth factor (VEGF) and VEGFR-2 expression. αv was suppressed by shRNA in HUVEC (venous endothelial cells) and HMVEC (microvascular endothelial cells).VEGFR-2 was significantly upregulated by αv suppression in HUVEC and downregulated in HMVEC at both mRNA and protein levels,as assessed by real-time PCR and flow cytometry,respectively.HMVEC displayed completely abolished Sp1 binding to the VEGFR-2 promoter, and HUVEC exhibited enhanced binding to the –170 E- Box element in the VEGFR-2 promoter, assessed by electrophoretic mobility shift assay. Realtime PCR also revealed opposite effects on the expression of 5 additional important genes involved in angiogenesis in the two cell types.VEGF mRNA expression was enhanced in HUVEC and reduced in HMVEC; however, these alterations were not statistically significant.VEGF-induced proliferation was upregulated in HUVEC and reduced in HMVEC following αv suppression. No tube formation on Matrigel was observed in αv suppressed cells, regardless of their origin.These results indicate that suppression of αv integrins can either augment or inhibit VEGFR-2 levels and VEGF-induced proliferation in EC from different vascular beds. Hence, therapeutic antiangiogenic intervention by siRN-Amediated suppression of αv integrins should take into account variable and potentially hazardous responses in different vascular beds.

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Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor

Journal of Cell Science ◽

10.1242/jcs.108.6.2369 ◽

1995 ◽

Vol 108 (6) ◽

pp. 2369-2379 ◽

Cited By ~ 24

Author(s):

W.G. Roberts ◽

G.E. Palade

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Intradermal Injection ◽

Microvascular Permeability ◽

Vascular Endothelial ◽

Vascular Permeability Factor ◽

Fenestrated Endothelium ◽

Vascular Beds ◽

Endothelial Growth Factor

The vascular endothelial growth factor (VEGF) was originally described as vascular permeability factor due to its ability to increase microvascular permeability to plasma proteins. However, the vessel types (arteriolar, venular, and capillary) affected by VEGF and the modification of endothelial morphology in response to increased permeability induced by VEGF in vivo have not been precisely documented. By topical application or intradermal injection of recombinant human VEGF-165 we find that VEGF increases the permeability of postcapillary venules as well as muscular venules and capillaries. Surprisingly, we also find that endothelia of small venules and capillaries become fenestrated within 10 minutes of VEGF application. Fenestrations appeared in vascular beds which do not normally have fenestrated endothelium, namely the cremaster muscle and skin. Histamine, saline, and heat-inactivated VEGF do not cause fenestrations. Increased permeability is completely inhibited when VEGF is cleared by immunoprecipitation with anti-VEGF monoclonal antibodies. The VEGF effect on permeability is unlike that of any other mediator described to date since both muscular venules and capillaries are affected.

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Vascular Endothelial Growth Factor (VEGF165) and its Influence on Angiogenesis versus Arteriogenesis in Different Vascular Beds

Journal of Endovascular Therapy ◽

10.1177/152660280200900619 ◽

2002 ◽

Vol 9 (6) ◽

pp. 842-854 ◽

Cited By ~ 3

Author(s):

Sigrid Nikol ◽

Jaroslav Pelisek ◽

Markus G. Engelmann ◽

Masumi Shimizu ◽

Alexandra Fuchs ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Coronary Arteries ◽

The Body ◽

Vascular Endothelial ◽

Peripheral Arteries ◽

Percutaneous Approach ◽

Vascular Beds ◽

Endothelial Growth Factor ◽

Specific Influence

Purpose: To use local gene delivery to determine any district-specific influence of vascular endothelial growth factor (VEGF165) on angiogenesis and arteriogenesis in arteries of distinct developmental origin. Methods: Coronary and peripheral arteries were chronically occluded in 30 Pietrain pigs using a percutaneous approach and blinded stent-graft. DNA was delivered to the adventitia in dosages corresponding to 10% of the body weight—adapted amount used in clinical trials. The coronary arteries in 12 animals and the peripheral arteries in 12 animals were treated or used as controls (no occlusion or occlusion with transfection of the β-galactosidase gene). Six additional animals were sacrificed at 1 or 3 weeks for expression analyses, while the other 24 animals were sacrificed at 5 months for expression analysis and histology. Angiography, polymerase chain reaction analyses, and immunohistochemistry were performed. Results: Expression of the VEGF gene was observed at 1 and 3 weeks following application, while transfected DNA was detected up to 5 months. New collaterals formed around occluded coronary arteries (2.63 ± 0.69 fold, p<0.05 versus 1.24 ± 0.40 fold for peripheral arteries), and angiographic arterial area increase was more pronounced in coronary (2.49 ± 0.59 fold, p<0.05) than peripheral arteries (1.49 ± 0.05 fold). There was no collateralization surrounding occluded peripheral arteries, but new arterial branches were seen (2.0 ± 0.28, p<0.05 versus 1.07 ± 0.31 for coronary). Conclusions: The response to VEGF, whether it is predominantly angiogenesis or arteriogenesis, is dependent on the target vessel. These observed differences in the behavior of arteries may be related to their differing developmental origins, which may have important implications for future therapeutic strategies using VEGF in different vessels.

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