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Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo

Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by microangiopathy with progressive loss of capillaries and tissue fibrosis. Imatinib exerts potent anti-fibrotic effects and is currently evaluated in clinical trials. The aim of the present study was to exclude that th...

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Autores principales: Venalis, Paulius, Maurer, Britta, Akhmetshina, Alfiya, Busch, Nicole, Dees, Clara, Stürzl, Michael, Zwerina, Jochen, Jüngel, Astrid, Gay, Steffen, Schett, Georg, Distler, Oliver, Distler, Jörg HW
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496125/
https://www.ncbi.nlm.nih.gov/pubmed/18774958
http://dx.doi.org/10.1111/j.1582-4934.2008.00492.x
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author Venalis, Paulius
Maurer, Britta
Akhmetshina, Alfiya
Busch, Nicole
Dees, Clara
Stürzl, Michael
Zwerina, Jochen
Jüngel, Astrid
Gay, Steffen
Schett, Georg
Distler, Oliver
Distler, Jörg HW
author_facet Venalis, Paulius
Maurer, Britta
Akhmetshina, Alfiya
Busch, Nicole
Dees, Clara
Stürzl, Michael
Zwerina, Jochen
Jüngel, Astrid
Gay, Steffen
Schett, Georg
Distler, Oliver
Distler, Jörg HW
author_sort Venalis, Paulius
collection PubMed
description Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by microangiopathy with progressive loss of capillaries and tissue fibrosis. Imatinib exerts potent anti-fibrotic effects and is currently evaluated in clinical trials. The aim of the present study was to exclude that the anti-fibrotic effects of imatinib are complicated by inhibitory effects on endothelial cell functions, which might augment vascular disease in SSc. Endothelial cells and mice were treated with pharmacologically relevant concentrations of imatinib. The expression of markers of vascular activation was assessed with real-time PCR. Proliferation was analysed with the cell counting experiments and the MTT assay. Apoptosis was quantified with caspase 3 assays, annexin V in vitro and with TUNEL staining in vivo. Migration was studied with scratch and transwell assays. Tube forming was investigated with the matrigel assay. Imatinib did not alter the expression of markers of vascular activation. Imatinib did not increase the percentage of annexin V positive cells or the activity of caspase 3. No reduction in proliferation or metabolic activity of endothelial cells was observed. Imatinib did not affect migration of endothelial cells and did not reduce the formation of capillary tubes. Consistent with the in vitro data, no difference in the number of apoptotic endothelial cells was observed in vivo in mice treated with imatinib. Imatinib does not inhibit activation, viability, proliferation, migration or tube forming of endothelial cells in vitro and in vivo. Thus, treatment with imatinib might not augment further endothelial cell damage in SSc.
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spelling pubmed-44961252015-07-13 Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo Venalis, Paulius Maurer, Britta Akhmetshina, Alfiya Busch, Nicole Dees, Clara Stürzl, Michael Zwerina, Jochen Jüngel, Astrid Gay, Steffen Schett, Georg Distler, Oliver Distler, Jörg HW J Cell Mol Med Articles Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by microangiopathy with progressive loss of capillaries and tissue fibrosis. Imatinib exerts potent anti-fibrotic effects and is currently evaluated in clinical trials. The aim of the present study was to exclude that the anti-fibrotic effects of imatinib are complicated by inhibitory effects on endothelial cell functions, which might augment vascular disease in SSc. Endothelial cells and mice were treated with pharmacologically relevant concentrations of imatinib. The expression of markers of vascular activation was assessed with real-time PCR. Proliferation was analysed with the cell counting experiments and the MTT assay. Apoptosis was quantified with caspase 3 assays, annexin V in vitro and with TUNEL staining in vivo. Migration was studied with scratch and transwell assays. Tube forming was investigated with the matrigel assay. Imatinib did not alter the expression of markers of vascular activation. Imatinib did not increase the percentage of annexin V positive cells or the activity of caspase 3. No reduction in proliferation or metabolic activity of endothelial cells was observed. Imatinib did not affect migration of endothelial cells and did not reduce the formation of capillary tubes. Consistent with the in vitro data, no difference in the number of apoptotic endothelial cells was observed in vivo in mice treated with imatinib. Imatinib does not inhibit activation, viability, proliferation, migration or tube forming of endothelial cells in vitro and in vivo. Thus, treatment with imatinib might not augment further endothelial cell damage in SSc. John Wiley & Sons, Ltd 2009-10 2008-09-04 /pmc/articles/PMC4496125/ /pubmed/18774958 http://dx.doi.org/10.1111/j.1582-4934.2008.00492.x Text en © 2008 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Articles
Venalis, Paulius
Maurer, Britta
Akhmetshina, Alfiya
Busch, Nicole
Dees, Clara
Stürzl, Michael
Zwerina, Jochen
Jüngel, Astrid
Gay, Steffen
Schett, Georg
Distler, Oliver
Distler, Jörg HW
Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo
title Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo
title_full Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo
title_fullStr Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo
title_full_unstemmed Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo
title_short Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo
title_sort lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496125/
https://www.ncbi.nlm.nih.gov/pubmed/18774958
http://dx.doi.org/10.1111/j.1582-4934.2008.00492.x
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