Nikita G. Nikiforov, Natalia V. Elizova, Michael Bukrinsky, Larisa Dubrovsky, Vsevolod J. Makeev, Yoshiyuki Wakabayashi, Poching Liu, Kathy K. Foxx, Howard S. Kruth, Xueting Jin, Emile R. Zakiev and Alexander N. Orekhov Pages 915 - 920 ( 6 )
In this mini-review, the role of macrophage phenotypes in atherogenesis is considered. Recent studies on distribution of M1 and M2 macrophages in different types of atherosclerotic lesions indicate that macrophages exhibit a high degree of plasticity of phenotype in response to various conditions in microenvironment. The effect of the accumulation of cholesterol, a key event in atherogenesis, on the macrophage phenotype is also discussed. The article presents the results of transcriptome analysis of cholesterol-loaded macrophages revealing genes involved in immune response whose expression rate has changed the most. It turned out that the interaction of macrophages with modified LDL leads to higher expression levels of pro-inflammatory marker TNF-α and antiinflammatory marker CCL18. Phenotypic profile of macrophage activation could be a good target for testing of novel anti-atherogenic immunocorrectors. A number of anti-atherogenic drugs were tested as potential immunocorrectors using primary macrophage-based model.
Atherosclerosis, macrophages, phenotype, transcriptome, activation, modified LDL, immunocorrectors, macrophage-based test.
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, GW School of Medicine and Health Sciences, George Washington University, 20037 Washington, DC, GW School of Medicine and Health Sciences, George Washington University, 20037 Washington, DC, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119333 Moscow, DNA Sequencing and Genomics Core, National Heart, Lung, and Blood Institute, National Institutes of Health, 20892 Bethesda, MD, DNA Sequencing and Genomics Core, National Heart, Lung, and Blood Institute, National Institutes of Health, 20892 Bethesda, MD, Kalen Biomedical, LLC, 20886 Montgomery Village, MD, Experimental Atherosclerosis Section, Center for Molecular, National Heart, Lung, and Blood Institute , National Institutes of Health, 20892 Bethesda, MD, Experimental Atherosclerosis Section, Center for Molecular, National Heart, Lung, and Blood Institute , National Institutes of Health, 20892 Bethesda, MD, INSERM UMR_S 1166, Faculte de Medecine Pitie-Salpetriere, University of Pierre and Marie Curie - Paris 6, 75013 Paris, Department of Biophysics, Biological Faculty, Moscow State University, Moscow 119991