RT Journal Article
SR Electronic
T1 173 Insulin-like growth factor binding protein 2 (igfbp2): a positive regulator of angiogenesis?
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP A121
OP A121
DO 10.1136/heartjnl-2017-311726.171
VO 103
IS Suppl 5
A1 Alexander-Francisco Bruns
A1 Jessica Smith
A1 Nadira Yuldasheva
A1 Mark T Kearney
A1 Stephen B Wheatcroft
YR 2017
UL http://heart.bmj.com/content/103/Suppl_5/A121.1.abstract
AB Introduction The insulin-like growth factor binding protein 2 (IGFBP2) has been implicated in the regulation of insulin-like growth factor (IGF) activity in most tissue and organs. IGFBP2 has, however, been reported to have additional intrinsic, IGF independent properties. Low circulating IGFBP2 levels are associated with obesity in humans. High levels of IGFBP2 on the other hand are linked to increased tumour angiogenesis in humans. In this setting increased angiogenesis has been suggested to be caused by indirect rather than direct modulation of endothelial cells. Here we tested the hypothesis that IGFBP2 is able to modulate endothelial cell function directly.Basic methods and Results Using immunoblotting, we show that acute stimulation of human umbilical vein endothelial cells (HUVEC) with 15 nM IGFBP2 lead to an increase in phosphorylation of Akt/PKB, an important regulator of endothelial cell function. Data obtained from an in vitro model of sprouting angiogenesis suggests that stimulation of HUVEC with IGFBP2 induced endothelial cell sprouting. Mice overexpressing human IGFBP2 showed increased tip cell formation and vascular density in the mouse retina model of developmental angiogenesis.Conclusions Here we present data from in vitro and in vivo models of angiogenesis supporting our hypothesis that IGFBP-2 is able to directly modulate endothelial cell function.