Role of guanylate binding protein‐1 in vascular defects associated with chronic inflammatory diseases |
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| Authors: | Matthias Hammon Martin Herrmann Oliver Bleiziffer Galyna Pryymachuk Laura Andreoli Luis E. Munoz Kerstin U. Amann Michele Mondini Marisa Gariglio Paolo Airó Vera S. Schellerer Antonis K. Hatzopoulos Raymund E. Horch Ulrich Kneser Michael Stürzl Elisabeth Naschberger |
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| Affiliation: | 1. Department of Plastic and Hand Surgery, University Medical Center Erlangen, Erlangen, Germany;2. Institute for Clinical Immunology and Rheumatology, Department for Internal Medicine 3, University Medical Center Erlangen, Erlangen, Germany;3. Rheumatology and Clinical Immunology, University Clinic of Brescia, Piazzale Spedali Civili, Brescia, Italy;4. Division of Nephropathology, Institute of Pathology, University Medical Center Erlangen, Erlangen, Germany;5. Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara, Italy;6. Department of Surgery, University Medical Center Erlangen, Erlangen, Germany;7. Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA;8. Division of Molecular and Experimental Surgery, Department of Surgery, University Medical Center Erlangen, Erlangen, Germany |
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| 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. |
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| Keywords: | rheumatic autoimmune disorders guanylate binding protein‐1 endothelial progenitor cells inflammation systemic lupus erythematosus rheumatoid arthritis systemic sclerosis |
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