Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation

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 supersatura...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	calciprotein particles endothelial dysfunction intimal hyperplasia vascular inflammation cardiovascular disease Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/843da48a9e81491cbdbe0edba3aa5f54
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spelling	oai:doaj.org-article:843da48a9e81491cbdbe0edba3aa5f542021-11-25T17:56:48ZCalciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation10.3390/ijms2222124581422-00671661-6596https://doaj.org/article/843da48a9e81491cbdbe0edba3aa5f542021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12458https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067An 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 Ca<sup>2+</sup>-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.Daria K. ShishkovaElena A. VelikanovaLeo A. BogdanovMaxim Yu. SinitskyAlexander E. KostyuninAnna V. TsepokinaOlga V. GruzdevaAndrey V. MironovRinat A. MukhamadiyarovTatiana V. GlushkovaEvgenia O. KrivkinaVera G. MatveevaOksana N. HryachkovaVictoria E. MarkovaYulia A. DylevaEkaterina V. BelikAlexey V. FrolovAmin R. ShabaevOlga S. EfimovaAnna N. PopovaValentina Yu. MalyshevaRoman P. KolmykovOleg G. SevostyanovDmitriy M. RussakovViatcheslav F. DolganyukAnton K. GutakovskyYuriy A. ZhivodkovAnton S. KozhukhovElena B. BrusinaZinfer R. IsmagilovOlga L. BarbarashArseniy E. YuzhalinAnton G. KutikhinMDPI AGarticlecalciprotein particlesendothelial dysfunctionintimal hyperplasiavascular inflammationcardiovascular diseaseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12458, p 12458 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	calciprotein particles endothelial dysfunction intimal hyperplasia vascular inflammation cardiovascular disease Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	calciprotein particles endothelial dysfunction intimal hyperplasia vascular inflammation cardiovascular disease Biology (General) QH301-705.5 Chemistry QD1-999 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 Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation
description	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 Ca<sup>2+</sup>-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.
format	article
author	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
author_facet	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
author_sort	Daria K. Shishkova
title	Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation
title_short	Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation
title_full	Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation
title_fullStr	Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation
title_full_unstemmed	Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation
title_sort	calciprotein particles link disturbed mineral homeostasis with cardiovascular disease by causing endothelial dysfunction and vascular inflammation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/843da48a9e81491cbdbe0edba3aa5f54
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Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation

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