Vascular calcification or ectopic calcification ofblood vessels forms an important
element of the increased cardiovascular risk observed in patients with
chronic kidney disease. In addition to the classical Framingham risk factors, specific
uremia-related factors such as
hyperphosphatemia and disturbed
calcium and
phosphorus metabolism contribute to the development of
vascular calcification. To gain a better insight into the mechanism of this calcification process, experimental techniques were developed to induce and detect
vascular calcification in rats with in vivo micro-CT imaging. By means of
synchrotron-based micro-X-ray diffraction the
mineral phase deposited in arteries of rats with
adenine-induced
chronic renal failure was found to consist mainly of
hydroxyapatite, whereas calcifications induced with high dose
vitamin D administration additionally contained
whitlockite, a
magnesium-containing
mineral.
Vascular calcification is an active, cell-regulated process. By immunohistochemically investigating the expression of bone-specific
proteins in calciying arteries, we demonstrated that calcifying vascular smooth muscle cells are not only able to acquire an osteoblast-like phenotype, but can moreover transdifferentiate to chondrocyte-like cells, expressing the cartilage
transcription factor sox9 and the cartilage
extracellular matrix protein collagen II. This cartilage phenotype was also found in human aortic tissue. Finally, treatment of uremic rats with the
calcium-free
phosphate binder
lanthanum carbonate was shown to inhibit the development of
vascular calcification, implying that adequate
phosphorus control without additional
calcium load reduces
vascular calcification. In the future, we will map the
proteome of calcifying vascular smooth muscle cells and investigate the paradoxical association of
vascular calcification with impaired bone mineralisation.