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
