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Invited researcher Leonid Borisovich Margolis
Contract number
14.B25.31.0016
Time span of the project
2013-2017
Head of the laboratory

As of 30.01.2020

29
Number of staff members
55
scientific publications
3
Objects of intellectual property
General information

Name of the project: Immune and viral mechanisms of atherosclerosis

Strategy for Scientific and Technological Development Priority Level: в


Goals and objectives

Research directions: Virology, immunology, tissue, cellular and molecular biology pathogenesis of atherosclerosis, determining immunological and virological mechanisms of formation and explosion of atherosclerotic plaques and development of new approaches to prevention of these pathological processes

Project objective: Determining immunological and virological mechanisms of formation and explosion of atherosclerotic plaques and developing new preventive and therapeutic approaches to atherosclerosis treatment


The practical value of the study

  • We have developed an original method for producing extracellular vesicles for biological and cultivated media. The method is based on conjugation with with magnetic nanoparticles and magnetic separation for their individual assessment using multicolor flow cytometry.
  • Using individual analysis we have for the first time that plasma of patients with coronary syndrome and healthy volunteers have different types of extracellular vesicles in their plasma.
  • Our researchers have demonstrated decrease of number of extracellular vesicles of thrombocytosis origin co-expressing СD31, CD63 and CD41 in patients with acute coronary syndrome against the background of antiaggregant therapy.
  • We have investigated change of state of endothelium in acute myocardial infarction patients and demonstrated positive impact of remote ischemic preconditioning on overcoming endothelial dysfunction.
  • Our team has demonstrated correlation between composition of endothelial extracellular vesicles and endothelium functioning.
  • We have optimized the method of producing immune cells from atherosclerotic plaque preserving their phenotypical individuality for further analysis of cellular composition of the plaque using multicolor flow cytometry.
  • A transformation of activated effector CD4+ and CD8+ of T-lymphocytes in atherosclerotic plaques compared to blood. THis can be one of the causes of destabilization of atherosclerotic plaques.
  • We have searched for causes of activation of T-lymphocytes in atherosclerotic plaques TO do this we we analyzed content of human herpes viruses (types 1-8) in blood, plasma, atherosclerotic plaques and intact regions of vessel walls. At least one type of human herpes virus was found in 93% samples.
  • From increase in abundance of DNA of cytomegaloviruses (CMV) in blood plasma we have inferred significant we have inferred significant predominance of active CMV infection in patients with acute coronary syndrome compared to healthy volunteers. We have found positive correlation with number of copies of CMV.
  • We have shown for the first time that presence of herpes virus in blood plasma (as a sign of activity of the virus in patients) correlates with number if lymphocytes of different degrees of differentiation in inflammation marker hs-CRP in patients with distributed atherosclerosis. Thus we have proven that cytomegalovirus activation leads to launch of active immune response that in turn can lead to growth and destabilization of atherosclerotic plaques increasing risk of development of an acute ischemic event.
  • The Laboratory has developed a 3D model and a method for cultivating explants of atherosclerotic plaques and determined change of their cellular composition in the process of cultivation. We have researched presence of different types of herpes viruses in plaques and cytokine profile in the cultivated environment.

Implemented results of research:

  • Patent of the Russian Federation No 2583940 «A method for determining composition of individual extracellular vesicles in human blood». Priority granted on 17 December 2014. Authors: Zh. Sh. Grivel, N. B. Ryzankina, M. S. Vagida, A. M. Lebedeva, O. I. Ivanova, L. B. Margolis, A.Arakelyan, Ye. Yu. Vasiliyeva.
  • Patent of the Russian Federation No 2616243 «A method for detecting cellular composition of atherosclerotic plaques». Priority granted on 10 December 2015. Authors: O. I. Ivanova, A. M. Lebedeva.
  • A patent application has been filed for a method of producing viral nucleic acids from different fractions of extracellular vesicles. Application No 218100803. Priority granted on 11 January 2018. Authors: A. M. Lebedeva, Ye. V. Maryukhich, O. I. Ivanova, M. S. Vagida, Ye. Yu. Vasiliyeva.
  • We have developed a series of primers and samples for assessing the extent of human herpes virus (types 1–8) from the number of DNA copies that can be determined using Image multiplex PCR.

Education and career development:

  • 5 candidate dissertations have been defended.
  • We have developed and launched 5 additional training programs for biologists and medical doctors of different specialization: «Membrane vesicles in atherosclerosis biology», «Immune mechanisms in pathogenesis of atherosclerosis», «Extracellular vesicules: normal condition and pathologies», «Biology of atherosclerosis»», «Viruses and extracellular vesicules», «Macrophages in pathologies» of atherosclerosis»».
  • We have developed lectures and practical lessons for the «Emergency cardiology» program.

Organizational and structural changes:

Research equipment of the Laboratory for conducting clinical tests is used jointly with the I. V. Davidovskiy City Clinical Hospital and in the education process at the Department of Cardiology of the A. I. Yevdokimov Moscow State University of Medicine and Dentistry.

Other results: The Laboratory regularly conducts lectures, seminars and conference that feature world class scientists. Highly qualified young researchers are involved in our work.

Collaborations:

  • Section on Intercellular Interactions of the Shriver National Maternal-Fetal Medicine, Imaging, and Behavioral Development of the National Institute of Health (USA): joint research, internships of employees, organizing conferences, seminars
  • Case Western University (USA), Higher School of Economics (Russia), N.F. Gamaleya Scientific Research Institute of Epidemiology and Microbiology of the Ministry of Health of Russia, MD Project 2000 (Russia), Tartis-Aging (Russia): joint research

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Lebedeva A., Vorobyeva D., Vagida M., Ivanova O., Felker E., Fitzgerald W., Danilova N., Gontarenko V., Shpektor A., Vasilieva E., Margolis L.
Ex vivo Culture of Human Atherosclerotic Plaques: A Model to Study Immune Cells in Atherogenesis. Atherosclerosis 267: 90–98 (2017).
Arakelyan A., Ivanova O., Vasilieva E., Grivel J.C., Margolis L.
Antigenic Composition of Single Nano-Sized Extracellular Blood Vesicles. Nanomedicine 11(3): 489–498 (2015).
Nikitskaya E., Lebedeva A., Ivanova O., Maryukhnich E., Shpektor A., Grivel J.-C., Margolis L., Vasilieva E.
Cytomegalovirus-Productive Infection is Associated with Acute Coronary Syndrome. Journal of the American Heart Association 5(8): e003759 (2016).
Vagida M., Arakelyan A., Lebedeva A., Grivel J.-C., Shpektor A., Vasilieva E., Margolis L.
Flow Analysis of Individual Blood Extracellular Vesicles in Acute Coronary Syndrome. Platelets 28(2): 165–173 (2017).
Vagida M., Arakelyan A., Lebedeva A., Grivel J.-C., Shpektor A., Vasilieva E., Margolis L.
Analysis of Еxtracellular Vesicles in Blood of Patients with Acute Coronary Syndrome Using Magnetic Nanoparticles. Biochemistry (Moscow) 81(4): 382–391 (2016).
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