TY - JOUR
T1 - Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases
AU - Hammon, Matthias
AU - Herrmann, Martin
AU - Bleiziffer, Oliver
AU - Pryymachuk, Galyna
AU - Andreoli, Laura
AU - Munoz, Luis E.
AU - Amann, Kerstin U.
AU - Mondini, Michele
AU - Gariglio, Marisa
AU - Airó, Paolo
AU - Schellerer, Vera S.
AU - Hatzopoulos, Antonis K.
AU - Horch, Raymund E.
AU - Kneser, Ulrich
AU - Stürzl, Michael
AU - Naschberger, Elisabeth
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - Endothelial progenitor cells
KW - Guanylate binding protein-1
KW - Inflammation
KW - Rheumatic autoimmune disorders
KW - Rheumatoid arthritis
KW - Systemic lupus erythematosus
KW - Systemic sclerosis
UR - http://www.scopus.com/inward/record.url?scp=79959460585&partnerID=8YFLogxK
U2 - 10.1111/j.1582-4934.2010.01146.x
DO - 10.1111/j.1582-4934.2010.01146.x
M3 - Article
SN - 1582-1838
VL - 15
SP - 1582
EP - 1592
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 7
ER -