Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization.
Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascula...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4100760?pdf=render |
| _version_ | 1818301877259862016 |
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| author | Jasmin Prüfer Mirjam Schuchardt Markus Tölle Nicole Prüfer Matthias Höhne Walter Zidek Markus van der Giet |
| author_facet | Jasmin Prüfer Mirjam Schuchardt Markus Tölle Nicole Prüfer Matthias Höhne Walter Zidek Markus van der Giet |
| author_sort | Jasmin Prüfer |
| collection | DOAJ |
| description | Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteo-chondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T05:29:59Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-43345bdcf64d43b7b226171acfac2db12022-12-21T23:58:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10170910.1371/journal.pone.0101709Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization.Jasmin PrüferMirjam SchuchardtMarkus TölleNicole PrüferMatthias HöhneWalter ZidekMarkus van der GietVascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteo-chondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis.http://europepmc.org/articles/PMC4100760?pdf=render |
| spellingShingle | Jasmin Prüfer Mirjam Schuchardt Markus Tölle Nicole Prüfer Matthias Höhne Walter Zidek Markus van der Giet Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization. PLoS ONE |
| title | Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization. |
| title_full | Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization. |
| title_fullStr | Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization. |
| title_full_unstemmed | Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization. |
| title_short | Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization. |
| title_sort | harmful effects of the azathioprine metabolite 6 mercaptopurine in vascular cells induction of mineralization |
| url | http://europepmc.org/articles/PMC4100760?pdf=render |
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