Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases.
J Cell Mol Med
; 15(7): 1582-92, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-20716116
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
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Proteínas de Ligação ao GTP
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Inflamação
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
J Cell Mol Med
Ano de publicação:
2011
Tipo de documento:
Article