BibTex format
@article{Bauer:2016:10.1038/srep29417,
author = {Bauer, A and Mylroie, H and Thornton, C and Calay, D and Birdsey, G and Kiprianos, A and Wilson, GK and Soares, MP and Yin, X and Mayr, M and Randi, A and Mason, JC},
doi = {10.1038/srep29417},
journal = {Scientific Reports},
title = {Identification of cyclins A1, E1 and vimentin as downstream targets of heme oxygenase-1 in vascular endothelial growth factor-mediated angiogenesis},
url = {http://dx.doi.org/10.1038/srep29417},
volume = {6},
year = {2016}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Angiogenesis is an essential physiological process and an important factor in diseasepathogenesis. However, its exploitation as a clinical target has achieved limited success and novelmolecular targets are required. Although heme oxygenase-1 (HO-1) acts downstream of vascularendothelial growth factor (VEGF) to modulate angiogenesis, knowledge of the mechanismsinvolved remains limited. We set out identify novel HO-1 targets involved in angiogenesis. HO-1depletion attenuated VEGF-induced human endothelial cell (EC) proliferation and tube formation.The latter response suggested a role for HO-1 in EC migration, and indeed HO-1 siRNA negativelyaffected directional migration of EC towards VEGF; a phenotype reversed by HO-1 overexpression.EC from Hmox1-/- mice behaved similarly. Microarray analysis of HO-1-depleted andcontrol EC exposed to VEGF identified cyclins A1 and E1 as HO-1 targets. Migrating HO-1-deficient EC showed increased p27, reduced cyclin A1 and attenuated cyclin-dependent kinase 2activity. In vivo, cyclin A1 siRNA inhibited VEGF-driven angiogenesis, a response reversed by AdHO-1.Proteomics identified structural protein vimentin as an additional VEGF-HO-1 target. HO-1depletion inhibited VEGF-induced calpain activity and vimentin cleavage, while vimentin silencingattenuated HO-1-driven proliferation. Thus, vimentin and cyclins A1 and E1 represent VEGFactivatedHO-1-dependent targets important for VEGF-driven angiogenesis.
AU - Bauer,A
AU - Mylroie,H
AU - Thornton,C
AU - Calay,D
AU - Birdsey,G
AU - Kiprianos,A
AU - Wilson,GK
AU - Soares,MP
AU - Yin,X
AU - Mayr,M
AU - Randi,A
AU - Mason,JC
DO - 10.1038/srep29417
PY - 2016///
SN - 2045-2322
TI - Identification of cyclins A1, E1 and vimentin as downstream targets of heme oxygenase-1 in vascular endothelial growth factor-mediated angiogenesis
T2 - Scientific Reports
UR - http://dx.doi.org/10.1038/srep29417
UR - http://hdl.handle.net/10044/1/33842
VL - 6
ER -