Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions

细胞凋亡介导的内皮毒性而非直接钙化或抗钙化蛋白的功能变化决定了磷酸钙生物体的致病作用

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作者:Anton G Kutikhin, Elena A Velikanova, Rinat A Mukhamadiyarov, Tatiana V Glushkova, Vadim V Borisov, Vera G Matveeva, Larisa V Antonova, Dmitriy E Filip'ev, Alexey S Golovkin, Daria K Shishkova, Andrey Yu Burago, Alexey V Frolov, Viktor Yu Dolgov, Olga S Efimova, Anna N Popova, Valentina Yu Malysheva

Abstract

Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease.

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