International Journal of Molecular Sciences (Nov 2021)
Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation
- Daria K. Shishkova,
- Elena A. Velikanova,
- Leo A. Bogdanov,
- Maxim Yu. Sinitsky,
- Alexander E. Kostyunin,
- Anna V. Tsepokina,
- Olga V. Gruzdeva,
- Andrey V. Mironov,
- Rinat A. Mukhamadiyarov,
- Tatiana V. Glushkova,
- Evgenia O. Krivkina,
- Vera G. Matveeva,
- Oksana N. Hryachkova,
- Victoria E. Markova,
- Yulia A. Dyleva,
- Ekaterina V. Belik,
- Alexey V. Frolov,
- Amin R. Shabaev,
- Olga S. Efimova,
- Anna N. Popova,
- Valentina Yu. Malysheva,
- Roman P. Kolmykov,
- Oleg G. Sevostyanov,
- Dmitriy M. Russakov,
- Viatcheslav F. Dolganyuk,
- Anton K. Gutakovsky,
- Yuriy A. Zhivodkov,
- Anton S. Kozhukhov,
- Elena B. Brusina,
- Zinfer R. Ismagilov,
- Olga L. Barbarash,
- Arseniy E. Yuzhalin,
- Anton G. Kutikhin
Affiliations
- Daria K. Shishkova
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Elena A. Velikanova
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Leo A. Bogdanov
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Maxim Yu. Sinitsky
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Alexander E. Kostyunin
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Anna V. Tsepokina
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Olga V. Gruzdeva
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Andrey V. Mironov
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Rinat A. Mukhamadiyarov
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Tatiana V. Glushkova
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Evgenia O. Krivkina
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Vera G. Matveeva
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Oksana N. Hryachkova
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Victoria E. Markova
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Yulia A. Dyleva
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Ekaterina V. Belik
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Alexey V. Frolov
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Amin R. Shabaev
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Olga S. Efimova
- Institute of Coal Chemistry and Material Science, Federal Research Center of Coal and Coal Chemistry, Siberian Branch of the Russian Academy of Sciences, 18 Sovetskiy Avenue, 650000 Kemerovo, Russia
- Anna N. Popova
- Institute of Coal Chemistry and Material Science, Federal Research Center of Coal and Coal Chemistry, Siberian Branch of the Russian Academy of Sciences, 18 Sovetskiy Avenue, 650000 Kemerovo, Russia
- Valentina Yu. Malysheva
- Institute of Coal Chemistry and Material Science, Federal Research Center of Coal and Coal Chemistry, Siberian Branch of the Russian Academy of Sciences, 18 Sovetskiy Avenue, 650000 Kemerovo, Russia
- Roman P. Kolmykov
- Institute of Coal Chemistry and Material Science, Federal Research Center of Coal and Coal Chemistry, Siberian Branch of the Russian Academy of Sciences, 18 Sovetskiy Avenue, 650000 Kemerovo, Russia
- Oleg G. Sevostyanov
- Institute of Fundamental Sciences, Kemerovo State University, 6 Krasnaya Street, 650000 Kemerovo, Russia
- Dmitriy M. Russakov
- Institute of Fundamental Sciences, Kemerovo State University, 6 Krasnaya Street, 650000 Kemerovo, Russia
- Viatcheslav F. Dolganyuk
- Institute of Fundamental Sciences, Kemerovo State University, 6 Krasnaya Street, 650000 Kemerovo, Russia
- Anton K. Gutakovsky
- Rzhanov Institute of Semiconductor Physics, Siberian Branch of the Russian Academy of Sciences, 13 Akademika Lavrentieva Avenue, 630090 Novosibirsk, Russia
- Yuriy A. Zhivodkov
- Rzhanov Institute of Semiconductor Physics, Siberian Branch of the Russian Academy of Sciences, 13 Akademika Lavrentieva Avenue, 630090 Novosibirsk, Russia
- Anton S. Kozhukhov
- Rzhanov Institute of Semiconductor Physics, Siberian Branch of the Russian Academy of Sciences, 13 Akademika Lavrentieva Avenue, 630090 Novosibirsk, Russia
- Elena B. Brusina
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Zinfer R. Ismagilov
- Institute of Coal Chemistry and Material Science, Federal Research Center of Coal and Coal Chemistry, Siberian Branch of the Russian Academy of Sciences, 18 Sovetskiy Avenue, 650000 Kemerovo, Russia
- Olga L. Barbarash
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Arseniy E. Yuzhalin
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- Anton G. Kutikhin
- Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
- DOI
- https://doi.org/10.3390/ijms222212458
- Journal volume & issue
-
Vol. 22,
no. 22
p. 12458
Abstract
An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.
Keywords
- calciprotein particles
- endothelial dysfunction
- intimal hyperplasia
- vascular inflammation
- cardiovascular disease