[Experimental study of the mechanism for vascular calcification in chronic kidney disease].
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.
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Laboratorium Pathofysiologie, Universiteit Antwerpen, Universiteitsplein 1, B 2610 Antwerpen.
D000818:Animals; D001031:Apatites / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D002114:Calcinosis / Q000209:etiology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D012307:Risk Factors; D013052:Spectrometry, X-Ray Emission; D014511:Uremia / Q000150:complications / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology* / Q000378:metabolism; D014961:X-Ray Diffraction
D001031:Apatites; D010710:Phosphates; D002118:Calcium