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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2009
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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. |
format | Online Article Text |
id | pubmed-4496125 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
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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