TY  - JOUR
A1  - Pruefer, Jasmin
A1  - Schuchardt, Mirjam
A1  - Toelle, Markus
A1  - Pruefer, Nicole
A1  - Hoehne, Matthias
A1  - Zidek, Walter
A1  - van der Giet, Markus
T1  - Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: Induction of mineralization
JF  - PLoS one
N2  - 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 osteochondrocyte-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.
Y1  - 2014
U6  - https://doi.org/10.1371/journal.pone.0101709
SN  - 1932-6203
VL  - 9
IS  - 7
PB  - PLoS
CY  - San Fransisco
ER  -