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The study of proinflammatory and anti-inflammatory cytokines and chemokines expression profiles in human monocytes to identify new effective biomarkers that have the best diagnostic potential in asymptomatic atherosclerosis.
This project is the first step in creating a method for assessing an individual activity of macrophages. The problems addressed in the project are socially significant because of the high incidence of life-threatening diseases and their effects in the population. The method of evaluation of monocyte-macrophages activity in human blood will be based on the analysis of expression of cytokines and chemokines - markers of inflammatory and anti-inflammatory activity of macrophages. The most informative panel of cytokines and chemokines obtained during the project can be further used to create effective diagnostic tests.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subclinical atherosclerosis | In vitro estimation of individual reactivity of monocytes in study participants with asymptomatic atherosclerotic plaques found in carotid arteries by ultrasound examination |
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| Healthy subjects | In vitro estimation of individual reactivity of monocytes in study participants without ultrasound signs of subclinical carotid atherosclerosis |
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| Diffuse intimal thickening | In vitro estimation of individual reactivity of monocytes in study participants with diffuse intima-media thickening of carotid arteries found at ultrasound examination |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| In vitro estimation of individual reactivity of monocytes | Other | Technique for isolation/separation of monocytes with culture purity more than 95 % CD14-positive cells according to flow cytometry, the share of viable cells at least 98% by trypan blue vital staining, capable of producing TNFa at concentration of at least 50 pg/ml when stimulated with 100 ng/ml IFN-gamma, and CCL18 at concentration at least 30 pg/ml when stimulated with 10 ng/ml interleukin. |
| Measure | Description | Time Frame |
|---|---|---|
| Development and optimization of the method of monocyte-macrophage isolation. | Technique for isolation/separation of monocytes with culture purity more than 95 % CD14-positive cells according to flow cytometry, the share of viable cells at least 98% by trypan blue vital staining, capable of producing TNFa at concentration of at least 50 pg/ml when stimulated with 100 ng/ml IFN-gamma, and CCL18 at concentration at least 30 pg/ml when stimulated with 10 ng/ml interleukin. | up to 1 years |
| Measure | Description | Time Frame |
|---|---|---|
| Sample processing and parameter measurements. | Creating a collection of samples of the culture medium during cell stimulation into pro-inflammatory or anti-inflammatory phenotype. Definition of individual profiles of cell activation by the production of proinflammatory and anti-inflammatory cytokines and chemokines (C5a, IL-4, IL-32 alpha, CD40 ligand, IL-5, CXCL10, G-CSF, IL-6, CXCL11/I-TAC, GM-CSF , IL-8, CCL2, CXCL1, IL-10, MIF, CCL1, IL-12 p70, CCL3, ICAM-1, IL-13, CCL4, IFN-gamma, IL-16, CCL5, IL-1 alpha, IL -17, CXCL12, IL-1 beta, IL-17E, Serpin E1, IL-1ra, TNF-alpha, IL-2, IL-27, and TREM-1). Database generation on individual reactivity of monocytes-macrophages from healthy donors, individuals predisposed to atherosclerosis, and patients with asymptomatic atherosclerosis. Creating a collection of samples. Determination of concentrations of pro-inflammatory and anti-inflammatory markers. |
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Inclusion Criteria:
Exclusion Criteria:
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The inclusion of healthy individuals, of apparently healthy persons with a predisposition to atherosclerosis, and subjects with subclinical atherosclerosis, according to the results of ultrasonographic examination of carotids, to achieve 80% statistical power (up to 50 study participants per group).
Conducting experiments on obtaining the individual cultures of blood monocytes and stimulation of cells by proinflammatory and anti-inflammatory stimuli
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| Name | Affiliation | Role |
|---|---|---|
| Alexander N Orekhov, PhD, DSc | Institute for Atherosclerosis Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute for Atherosclerosis Research | Moscow | 121609 | Russia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23438959 | Background | Gratchev A, Ovsiy I, Manousaridis I, Riabov V, Orekhov A, Kzhyshkowska J. Novel monocyte biomarkers of atherogenic conditions. Curr Pharm Des. 2013;19(33):5859-64. doi: 10.2174/1381612811319330004. | |
| 22325375 | Background | Gratchev A, Sobenin I, Orekhov A, Kzhyshkowska J. Monocytes as a diagnostic marker of cardiovascular diseases. Immunobiology. 2012 May;217(5):476-82. doi: 10.1016/j.imbio.2012.01.008. Epub 2012 Jan 13. |
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| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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Whole blood taken with anticoagulants for immediate monocyte isolation to be seeded in cell culture, and for preparation of plasma samples to be frozen for lipid analysis.
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| up to 1 years |