ABSTRACTS: 1
Implication of soluble receptors of VEGF, sVEGFR-1 and sVEGFR-2, in angiogenesis

4TH EMBIC SUMMER SCHOOL, BARCELONA, SPAIN, 2TH -6TH JUNE 2008 TOP SELECTED ABSTRACTS

Authors


Abstract

Introduction:  sVEGFR-1 and sVEGFR-2 are soluble forms of the membrane-bound receptors of VEGF. sVEGFR-1 is detected in plasma of pre-eclamptic women, during ischemia and in some cancer cases. sVEGFR-2, was recently detected in plasma of healthy people, in leukaemia and in systemic erythematosus lupus cases. sVEGFR-1 has anti-angiogenic properties in vitro and in vivo but sVEGFR-2 remains uncharacterized and its physiological or pathological role is still unknown.

Material and Methods:  The aim of this study was to understand and to characterize the role of sVEGFR2 in angiogenesis and in endothelial function.

Results:  In aortic ring assay, an ex vivo model of angiogenesis, sVEGFR1 and sVEGFR2 were able to abolish VEGF-induced angiogenesis. However, when used alone, they induced the formation of a “network”, supposed to be vascular in visible microscopy. As they were able to abolish the effect of VEGF on endothelial function but showed no direct effect alone, we performed an immuno-staining of the “vascular network” induced by the soluble receptors. It showed that there were a few endothelial cells but mostly pericytes/smooth muscle cells (PC/SMC). Our first in vitro experiments on PC/SMC showed that sVEGFR-1 and sVEGFR-2 were able to promote the migration of PC/SMC, only in presence of endothelial cells.

Conclusions:  Our results evidence that sVEGFR1 and sVEGFR2 inhibit VEGF-induced angiogenesis in a similar way. However, they have also a direct effect on PC/SMC, promoting their migration. Our results suggest that these soluble receptors could act, not only on endothelial cells themselves, but by a direct effect on PC/SMC too. These results contribute to identify factors by which it could be possible to regulate the balance between pro-angiogenic and anti-angiogenic factors, especially in the case of the anti-VEGF drugs used now as anti-cancer therapies in clinics, where a transient “normalization” of the vessels is observed.

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