Quantification of the initial levels of calciprotein particles as a screening marker of mineral homeostasis in patients with cardiovascular disease and in patients with chronic kidney disease

Шишкова, Д. К.; Матвеева, В. Г.; Marková, V.; Hryachkova, O. N.; Индукаева, Е. В.; Шабаев, А. Р.; Фролов, А В; Kutikhin, Anton G.

doi:10.15829/1560-4071-2022-5064

Russ J Cardiol

2023

DOI: 10.15829/1560-4071-2022-5064

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Quantification of the initial levels of calciprotein particles as a screening marker of mineral homeostasis in patients with cardiovascular disease and in patients with chronic kidney disease

Д. К. Шишкова

В. Г. Матвеева

V. Marková

et al.

Abstract: Aim. To evaluate the initial concentration of calciprotein particles (CPPs), which are scavengers of excessive calcium and phosphate, in patients with cardiovascular disease and in patients with chronic kidney disease as compared with the healthy volunteers.Material and methods. The study included 308 individuals as follows: 1) 88 participants of the PURE study without hemodynamically relevant carotid athero scle rosis and symptomatic coronary atherosclerosis; 2) 88 patients with cere brovascular disease (CVD)… Show more

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2024

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Cited by 3 publications

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Patterns of Calcium Distribution by Biochemical Serum Compartments in Vitro Modeling of Mineral Stress in the Context of Endothelial Dysfunction

Shishkova,

Markova,

Markova

et al. 2024

Kompleks. probl. serdečno-sosud. zabol.

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HighlightsWhen modeling mineral stress, a closed biochemical system shows the following calcium distribution ratio among biochemical compartments: freely circulating ions (Ca2+) – 50%, bound to albumin (CPM) - 20%, bound to and phosphorus (CPC) - 30%.The ratio of ionized to protein- or phosphorus-bound calcium was 1:1 and corresponded to the physiological ratio of ionized to bound calcium in circulating blood, indicating the physiological relevance of the simulations performed.Even under supraphysiological mineral stress, natural mineral depots (CPM and HRC) maintain the calcium-binding capacity of the biochemical system at the physiological level (50%), and the ratio of the relative calcium capacity of the CPM and HRC under conditions of supraphysiological mineral stress indicates the priority role of the HRC as a buffer system limiting the uncontrolled increase in ionized calcium in case of disturbance of the mineral balance of the blood. AbstractAim. To conduct a comparative analysis of calcium content in various biochemical compartments: 1) ionized (freely circulating, unbound) calcium; 2) calcium-albumin CPM (protein-bound calcium); 3) calcium phosphorus complexes (CPC).Methods. In order to prepare a biochemical system for the parallel synthesis of CPM and CPC, supraphysiological mineral stress was modeled by supersaturating a NaCl saline solution containing a physiological concentration of albumin with calcium (CaCl2) and phosphorus (Na2HPO4) ions. Separation of calcium-containing biochemical compartments was carried out by ultracentrifugation (to isolate CPM) and ultrafiltration (to separate CPM and the pool of free ions). Calcium concentration was measured using a colorimetric method based on the reaction of orthocresolphthalein complexone with calcium ions in an alkaline medium.Results. When modeling mineral stress, a closed biochemical system was obtained in which calcium ions were freely distributed in three states: circulating in free form (Ca2+) or being part of the CPM (colloidal primary depot) or PSC (corpuscular secondary depot). The distribution of calcium in the form of freely circulating ions (Ca2+) and when bound to albumin (CPM) and phosphorus (CPC) was 50%: 20%: 30% (5: 2: 3), respectively. The ratio of ionized to protein- or phosphorus-bound calcium was 1:1 and corresponded to the physiological ratio of ionized to bound calcium in circulating blood, indicating the physiological relevance of the simulations performed. The formation of HRC absorbed 10 to 20% of the total albumin.Conclusion. Even under supraphysiological mineral stress, natural mineral depots (CPM and HRC) maintain the calcium-binding capacity of the biochemical system at the physiological level (50%), and the ratio of the relative calcium capacity of the CPM and HRC under conditions of supraphysiological mineral stress indicates the priority role of the HRC as a buffer system limiting the uncontrolled increase in ionized calcium in case of disturbance of the mineral balance of the blood.

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Patterns of Calcium Distribution by Biochemical Serum Compartments in Vitro Modeling of Mineral Stress in the Context of Endothelial Dysfunction

Shishkova,

Markova,

Markova

et al. 2024

Kompleks. probl. serdečno-sosud. zabol.

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Pathological Effects of Ionized Calcium, Calciprotein Monomers and Calciprotein Particles on Arterial Endothelial Cells

Shishkova,

Markova,

Markova

et al. 2024

Kompleks. probl. serdečno-sosud. zabol.

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HighlightsTo achieve a 10% (i.e., 1.1-fold) increase in ionized calcium level in the serum-free cell culture medium and Wistar rat serum, 10 µg/mL calcium (e.g. with CaCl2) should be added; this corresponds to the upper quartile of ionized calcium in the human population.Incubation with ionized calcium or calciprotein monomers (10 µg/mL calcium) does not induce any pathological effects in primary arterial endothelial cells, although calciprotein monomers are internalised by endothelial cells similar to calciprotein particles.Incubation of primary human coronary artery endothelial cells with calciprotein particles (10 µg/mL calcium) triggers an increased expression of VCAM1, ICAM1, and SELE genes (i.e., those encoding cell adhesion molecules) as well as IL6, CXCL8, and CXCL1 genes (i.e., those encoding pro-inflammatory cytokines), together indicating endothelial activation. Aim. To compare the pathological effects of ionized calcium, calciprotein monomers (CPMs), and calciprotein particles (CPPs) after their addition to endothelial cells.Methods. CPMs and CPPs were synthesized by the supersaturation of albumin-supplemented NaCl solution with calcium (by adding CaCl2) and phosphate ions (by adding Na2HPO4). CPMs and CPPs were separated by sequential ultracentrifugation (to isolate CPPs) and ultrafiltration (to separate CPMs and free mineral ions). Calcium concentration in CPMs and CPPs was measured by an o-cresolphthalein complexone-based colorimetric assay. Internalization of fluorescent-labeled CPMs and CPPs by endothelial cells was interrogated by confocal microscopy after their 1-hour co-incubation under flow. Primary coronary artery and internal thoracic artery endothelial cells were incubated with ionized calcium (CaCl2), CPMs, or CPPs (10 µg/mL calcium) upon reaching confluence (n = 6 wells per group) to simulate a 10% increase in ionized calcium concentration. After 24 hours, we collected RNA and analyzed the gene expression pattern by reverse transcription-quantitative polymerase chain reaction.Results. CPMs and CPPs were internalized by endothelial cells as soon as after 1 hour of co-incubation under flow. Treatment with ionized calcium or CPMs (10 µg/mL calcium) did not cause any pathological effects in arterial endothelial cells. In contrast, CPPs promoted an expression of VCAM1, ICAM1, and SELE genes (i.e., those encoding cell adhesion molecules) as well as IL6, CXCL8, and CXCL1 genes (i.e., those encoding pro-inflammatory cytokines) in primary human coronary artery endothelial cells, together indicating their pro-inflammatory activation.Conclusion. Pathological effects of calcium stress are defined by the calcium source and not simply by its concentration.

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Associations of the variable site rs2010963 of the VEGF-A gene with multifocal atherosclerosis in aluminum industry workers with chronic occupational intoxication with fluoride compounds

Yadykina,

Korotenko,

Kazitskaya

et al. 2024

Hygiene and Sanitation

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Introduction. The aluminum industry occupies a leading position among non-ferrous metallurgy industries in revealing somatic pathologies in workers that occur against the background of chronic fluoride intoxication. Long-term exposure to fluorides on the body has a cardiovasotoxic effect, leads to structural and functional disorders of the myocardium and the development of comorbid cardiovascular pathology. This dictates the need for a risk-oriented approach to its diagnosis, including one based on molecular genetic analysis, for the timely identification of risk groups for the development of atherosclerosis and the elaboration of preventive measures aimed at preserving the health and maintaining working longevity of the studied occupational cohort. Materials and methods. There were examined ninety seven metallurgists with a previously proven diagnosis of chronic occupational intoxication with fluoride compounds, engaged in aluminum production. The comparison group consisted of 33 workers of this enterprise without a proven occupational disease. All respondents underwent ultrasound investigation of the main arteries. Genotyping of the rs2010963 polymorphic locus of the VEGF-A gene was carried out in a 96-well format using TaqMan technology (allele-specific real-time PCR). Results. The associative connection of the G/G VEGF-A genotype is determined in metallurgists with the risk of developing chronic occupational intoxication with fluoride compounds and heterozygous G/C genotype in subjects with multifocal atherosclerosis. The high level of predictive value of the polymorphism -634 G/C (rs2010963) of the VEGF-A gene allows considering it a marker of the risk for the developing atherosclerosis in workers exposed to long-term impact to fluoride compounds on the body. Limitations. The study was limited to the number of long-term work experienced subjects undergoing periodic medical examinations and undergoing inpatient treatment at the Research Institute for Complex Problems of Hygiene and Occupational Diseases. Conclusion. It is recommended to conduct a screening molecular and genetic analysis in a clinical hospital setting for timely assessment of the prognostic significance of risk markers for the development of atherosclerosis and its complications in workers of basic occupations engaged in aluminum production.

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Quantification of the initial levels of calciprotein particles as a screening marker of mineral homeostasis in patients with cardiovascular disease and in patients with chronic kidney disease

Cited by 3 publications

References 16 publications

Patterns of Calcium Distribution by Biochemical Serum Compartments in Vitro Modeling of Mineral Stress in the Context of Endothelial Dysfunction

Patterns of Calcium Distribution by Biochemical Serum Compartments in Vitro Modeling of Mineral Stress in the Context of Endothelial Dysfunction

Pathological Effects of Ionized Calcium, Calciprotein Monomers and Calciprotein Particles on Arterial Endothelial Cells

Associations of the variable site rs2010963 of the VEGF-A gene with multifocal atherosclerosis in aluminum industry workers with chronic occupational intoxication with fluoride compounds

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