Open AccessRole of guanylate binding protein‐1 in vascular defects associated with chronic inflammatory diseases
Author(s) -
Hammon Matthias,
Herrmann Martin,
Bleiziffer Oliver,
Pryymachuk Galyna,
Andreoli Laura,
Munoz Luis E.,
Amann Kerstin U.,
Mondini Michele,
Gariglio Marisa,
Airó Paolo,
Schellerer Vera S.,
Hatzopoulos Antonis K.,
Horch Raymund E.,
Kneser Ulrich,
Stürzl Michael,
Naschberger Elisabeth
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01146.x
Subject(s) - von willebrand factor , in vivo , progenitor cell , inflammation , endothelial progenitor cell , immunology , downregulation and upregulation , in vitro , chemistry , biology , microbiology and biotechnology , stem cell , platelet , biochemistry , gene
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.