VASCULAR ENDOTHELIAL GROWTH-FACTOR INCREASES RELEASE OF GELATINASE-A AND DECREASES RELEASE OF TISSUE INHIBITOR OF METALLOPROTEINASES BY MICROVASCULAR ENDOTHELIAL-CELLS IN-VITRO
Wj. Lamoreaux et al., VASCULAR ENDOTHELIAL GROWTH-FACTOR INCREASES RELEASE OF GELATINASE-A AND DECREASES RELEASE OF TISSUE INHIBITOR OF METALLOPROTEINASES BY MICROVASCULAR ENDOTHELIAL-CELLS IN-VITRO, Microvascular research, 55(1), 1998, pp. 29-42
The present study was designed to determine the influences of vascular
endothelial growth factor (VEGF) on cell proliferation and the releas
e of matrix metalloproteinases (MMPs) and tissue inhibitors of metallo
proteinases (TIMPs) from human dermal microvascular endothelial cells.
Treatment of cultures with 10 ng/ml or more of VEGF significantly inc
reased cell proliferation. The effect of VEGF treatment on the levels
of specific MMPs and TIMPs in the media was subsequently examined in c
ultures that were treated with 10 ng/ml VEGF. Zymography and Western b
lot analyses demonstrated that gelatinase A levels in the media were i
ncreased by VEGF treatment. Collagenase was detected by Western blots
in both VEGF-treated and untreated culture media, but the levels were
not significantly increased by the VEGF treatment. An ELISA assay conf
irmed that VEGF treatment significantly increased gelatinase A levels
but did not significantly increase collagenase levels. Western blot an
d ELISA data showed that VEGF treatment significantly decreased TIMP-1
and TIMP-2 levels compared to untreated cultures. The data suggest th
at VEGF may modulate endothelial cell-derived MMP activity by: (1) inc
reasing the abundance of gelatinase A; (2) disinhibiting gelatinase A
by decreasing the abundance of TIMP-2; and (3) disinhibiting preexisti
ng collagenase by reducing levels of TIMP-1. These actions could contr
ibute to the ability of VEGF to promote endothelial cell invasion of n
ew territory. (C) 1998 Academic Press.