Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases.
Rheumatic autoimmune disorders are characterized by a sustained pro-inflammatory microenvironment associated with impaired function of endothelial progenitor cells (EPC) and concomitant vascular defects. Guanylate binding protein-1 (GBP-1) is a marker and intracellular regulator of the inhibition of proliferation, migration and invasion of endothelial cells induced by several pro-inflammatory cytokines. In addition, GBP-1 is actively secreted by endothelial cells. In this study, significantly increased levels of GBP-1 were detected in the sera of patients with chronic inflammatory disorders. Accordingly we investigated the function of GBP-1 in EPC. Interestingly, stable expression of GBP-1 in T17b EPC induced premature differentiation of these cells, as indicated by a robust up-regulation of both Flk-1 and von Willebrand factor expression. In addition, GBP-1 inhibited the proliferation and migration of EPC in vitro. We confirmed that GBP-1 inhibited vessel-directed migration of EPC at the tissue level using the rat arterio-venous loop model as a novel quantitative in vivo migration assay. Overall, our findings indicate that GBP-1 contributes to vascular dysfunction in chronic inflammatory diseases by inhibiting EPC angiogenic activity via the induction of premature EPC differentiation.
Hammon
Matthias
M
Department of Plastic and Hand Surgery, University Medical Center Erlangen, Schwabachanlage 10, Erlangen, Germany.
Herrmann
Martin
M
Bleiziffer
Oliver
O
Pryymachuk
Galyna
G
Andreoli
Laura
L
Munoz
Luis E
LE
Amann
Kerstin U
KU
Mondini
Michele
M
Gariglio
Marisa
M
Airó
Paolo
P
Schellerer
Vera S
VS
Hatzopoulos
Antonis K
AK
Horch
Raymund E
RE
Kneser
Ulrich
U
Stürzl
Michael
M
Naschberger
Elisabeth
E
D000328:Adult; D000368:Aged; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D002908:Chronic Disease; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008875:Middle Aged; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
C490287:GBP1 protein, human; D019204:GTP-Binding Proteins