title: Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions.
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.
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Anton G
authors.initials: AG
authors.lastname: Kutikhin
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Velikanova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Rinat A
authors.initials: RA
authors.lastname: Mukhamadiyarov
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Glushkova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Borisov
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Vera G
authors.initials: VG
authors.lastname: Matveeva
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Antonova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Dmitriy E
authors.initials: DE
authors.lastname: Filip'ev
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Alexey S
authors.initials: AS
authors.lastname: Golovkin
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Daria K
authors.initials: DK
authors.lastname: Shishkova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Andrey Yu
authors.initials: AY
authors.lastname: Burago
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Frolov
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.
authors.forename: Viktor Yu
authors.initials: VY
authors.lastname: Dolgov
authors.affiliation: Institute of Coal Chemistry and Material Science under the Siberian Branch of the Russian Academy of Sciences, Sovietsky Avenue 18, Kemerovo, 650000, Russian Federation.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Efimova
authors.affiliation: Institute of Coal Chemistry and Material Science under the Siberian Branch of the Russian Academy of Sciences, Sovietsky Avenue 18, Kemerovo, 650000, Russian Federation.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Popova
authors.affiliation: Institute of Coal Chemistry and Material Science under the Siberian Branch of the Russian Academy of Sciences, Sovietsky Avenue 18, Kemerovo, 650000, Russian Federation.
authors.forename: Valentina Yu
authors.initials: VY
authors.lastname: Malysheva
authors.affiliation: Institute of Coal Chemistry and Material Science under the Siberian Branch of the Russian Academy of Sciences, Sovietsky Avenue 18, Kemerovo, 650000, Russian Federation.
authors.forename: Alexandr A
authors.initials: AA
authors.lastname: Vladimirov
authors.affiliation: Institute of Coal Chemistry and Material Science under the Siberian Branch of the Russian Academy of Sciences, Sovietsky Avenue 18, Kemerovo, 650000, Russian Federation.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Sozinov
authors.affiliation: Institute of Coal Chemistry and Material Science under the Siberian Branch of the Russian Academy of Sciences, Sovietsky Avenue 18, Kemerovo, 650000, Russian Federation.
authors.forename: Zinfer R
authors.initials: ZR
authors.lastname: Ismagilov
authors.affiliation: Kemerovo State University, Krasnaya Street 6, Kemerovo, 650043, Russian Federation.
authors.forename: Dmitriy M
authors.initials: DM
authors.lastname: Russakov
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine under the Siberian Branch of the Russian Academy of Sciences, Lavrentiev Avenue 8, Novosibirsk, 630090, Russian Federation.|Novosibirsk State University, Pirogova Street 2, Novosibirsk, 630090, Russian Federation.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Lomzov
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine under the Siberian Branch of the Russian Academy of Sciences, Lavrentiev Avenue 8, Novosibirsk, 630090, Russian Federation.|Novosibirsk State University, Pirogova Street 2, Novosibirsk, 630090, Russian Federation.
authors.forename: Dmitriy V
authors.initials: DV
authors.lastname: Pyshnyi
authors.affiliation: Rzhanov Institute of Semiconductor Physics under the Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentieva 13, Novosibirsk, 630090, Russian Federation.
authors.forename: Anton K
authors.initials: AK
authors.lastname: Gutakovsky
authors.affiliation: Rzhanov Institute of Semiconductor Physics under the Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentieva 13, Novosibirsk, 630090, Russian Federation.
authors.forename: Yuriy A
authors.initials: YA
authors.lastname: Zhivodkov
authors.affiliation: Institute of Cytology and Genetics under the Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentieva 10, Novosibirsk, 630090, Russian Federation.
authors.forename: Evgeniy A
authors.initials: EA
authors.lastname: Demidov
authors.affiliation: Novosibirsk State University, Pirogova Street 2, Novosibirsk, 630090, Russian Federation.|Institute of Cytology and Genetics under the Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentieva 10, Novosibirsk, 630090, Russian Federation.
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Peltek
authors.affiliation: Research Institute of Biotechnology, Kemerovo Institute of Food Science and Technology, Stroiteley Boulevard 47, Kemerovo, 650056, Russian Federation.
authors.forename: Viatcheslav F
authors.initials: VF
authors.lastname: Dolganyuk
authors.affiliation: Research Institute of Biotechnology, Kemerovo Institute of Food Science and Technology, Stroiteley Boulevard 47, Kemerovo, 650056, Russian Federation.
authors.forename: Olga O
authors.initials: OO
authors.lastname: Babich
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.|Kemerovo State Medical Academy, Voroshilova Street 22a, Kemerovo, 650029, Russian Federation.
authors.forename: Evgeniy V
authors.initials: EV
authors.lastname: Grigoriev
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.|Kemerovo State Medical Academy, Voroshilova Street 22a, Kemerovo, 650029, Russian Federation.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Brusina
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.|Kemerovo State Medical Academy, Voroshilova Street 22a, Kemerovo, 650029, Russian Federation.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Barbarash
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo, 650002, Russian Federation.|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.
authors.forename: Arseniy E
authors.initials: AE
authors.lastname: Yuzhalin
mesh_terms: D017209:Apoptosis; D040761:Biomimetic Materials / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D002130:Calcium Phosphates / Q000633:toxicity*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D010710:Phosphates / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000737:chemistry*; D012492:Salts / Q000378:metabolism
chemical_list: D002130:Calcium Phosphates; D010710:Phosphates; D012492:Salts; C020243:calcium phosphate