کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1938884 | 1050749 | 2007 | 7 صفحه PDF | دانلود رایگان |
VEGF165 is a key regulator of angiogenesis and a potent vascular permeability factor. Using snake venom proteins as tools, we demonstrate the enhanced vascular leakage of VEGF by KDR-binding proteins. The snake venom-derived KDR-specific VEGF, vammin, potently enhanced vascular leakage compared with other known permeability-enhancing factors including VEGF165, while KDR-bp from snake venom, a KDR antagonist of endothelial cell growth was a very weak permeability enhancer. Unexpectedly when co-administrated, KDR-bp synergistically enhanced either vammin or VEGF165-stimulated vascular leakage, despite its antagonistic effect on cell growth. This augmenting effect was specifically observed in the combined administration of KDR-bp with either VEGF165 or vammin, but not other combination of known permeability-enhancing factors. We further demonstrated a similar increased vascular leakage by the combined administration of VEGF165 and TIMP-3, the only known endogenous antagonist of KDR. Our findings implicate TIMP-3 as a critical player in the vascular leakage-enhancing effect of VEGF165 in vivo.
Journal: Biochemical and Biophysical Research Communications - Volume 355, Issue 3, 13 April 2007, Pages 693–699