Monocyte Activation in Preclinical Atherosclerosis

Overview

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.

Full Title of Study: “Cross-sectional Clinical Study of the Individual Profile of Activation of Circulating Blood Monocytes in Subjects With Preclinical Atherosclerosis.”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Cross-Sectional
  • Study Primary Completion Date: April 2014

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

  • Other: In 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.

Arms, Groups and Cohorts

  • Subclinical atherosclerosis
    • In vitro estimation of individual reactivity of monocytes in study participants with asymptomatic atherosclerotic plaques found in carotid arteries by ultrasound examination
  • Healthy subjects
    • In vitro estimation of individual reactivity of monocytes in study participants without ultrasound signs of subclinical carotid atherosclerosis
  • 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

Clinical Trial Outcome Measures

Primary Measures

  • Development and optimization of the method of monocyte-macrophage isolation.
    • Time Frame: 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 Measures

  • Sample processing and parameter measurements.
    • Time Frame: 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: 79 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Institute for Atherosclerosis Research, Russia
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Alexander N Orekhov, PhD, DSc, Principal Investigator, Institute for Atherosclerosis Research

References

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.

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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