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Sci Rep. 2016 Jun 2;6:27255. doi: 10.1038/srep27255.

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

Author information

1
Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
2
Institute of Coal Chemistry and Material Science under the Siberian Branch of the Russian Academy of Sciences, Sovietsky Avenue 18, Kemerovo, 650000, Russian Federation.
3
Kemerovo State University, Krasnaya Street 6, Kemerovo, 650043, Russian Federation.
4
Institute of Chemical Biology and Fundamental Medicine under the Siberian Branch of the Russian Academy of Sciences, Lavrentiev Avenue 8, Novosibirsk, 630090, Russian Federation.
5
Novosibirsk State University, Pirogova Street 2, Novosibirsk, 630090, Russian Federation.
6
Rzhanov Institute of Semiconductor Physics under the Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentieva 13, Novosibirsk, 630090, Russian Federation.
7
Institute of Cytology and Genetics under the Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentieva 10, Novosibirsk, 630090, Russian Federation.
8
Research Institute of Biotechnology, Kemerovo Institute of Food Science and Technology, Stroiteley Boulevard 47, Kemerovo, 650056, Russian Federation.
9
Kemerovo State Medical Academy, Voroshilova Street 22a, Kemerovo, 650029, Russian Federation.
10
Department of Oncology, Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, OX3 7DQ, Oxford, United Kingdom.

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.

PMID:
27251104
PMCID:
PMC4890115
DOI:
10.1038/srep27255
[Indexed for MEDLINE]
Free PMC Article

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