Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases.

Hammon M, Herrmann M, Bleiziffer O, Pryymachuk G, Andreoli L, Munoz LE, Amann KU, Mondini M, Gariglio M, Airó P, Schellerer VS, Hatzopoulos AK, Horch RE, Kneser U, Stürzl M, Naschberger E
J Cell Mol Med. 2011 15 (7): 1582-92

PMID: 20716116 · PMCID: PMC3823202 · DOI:10.1111/j.1582-4934.2010.01146.x

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.

© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

MeSH Terms (17)

Adult Aged Animals Autoimmune Diseases Cell Differentiation Cell Movement Chronic Disease Endothelial Cells Endothelium, Vascular Female GTP-Binding Proteins Humans Inflammation Mice Middle Aged Rats Stem Cells

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