Atherosclerosis
Conditions
Keywords
proinflammatory cytokines, anti-inflammatory cytokines, human monocytes, activation, biomarkers, asymptomatic atherosclerosis
Brief summary
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.
Detailed description
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.
Interventions
OTHERIn vitro estimation of individual reactivity of monocytes
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.
Sponsors
Institute for Atherosclerosis Research, Russia
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
40 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
* men and women aged 40 to 74 years * arterial normotension or mild arterial hypertension (systolic blood pressure \<160 mm Hg, diastolic blood pressure \<90 mm Hg) * absence of chronic diseases demanding permanent drug administration (more than 2 month per year)
Exclusion criteria
* personal history of transient ischemic attacks * personal history of chronic diseases demanding permanent drug administration (more than 2 month per year) * personal history of life-threatening diseases * indications for surgical treatment of atherosclerotic lesions localized in the extracranial brachiocephalic system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development and optimization of the method of monocyte-macrophage isolation. | up to 1 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sample processing and parameter measurements. | up to 1 years | 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. |
Countries
Russia
Outcome results
None listed