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An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization
Published on: June 12, 2013
Use of Primary Macrophages for Searching Novel Immunocorrectors
Nikita G Nikiforov1, Natalia V Elizova1, Michael Bukrinsky2
1Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russian Federation.
Abstract:
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.
Insights
Macrophages exhibit plasticity in atherosclerosis, with cholesterol influencing their M1/M2 phenotypes. This study identifies key immune genes and explores potential immunocorrectors for treating atherosclerosis.
Area of Science:
- Cardiovascular Research
- Immunology
- Molecular Biology
Background:
- Atherosclerosis involves complex macrophage phenotypes.
- Macrophage plasticity is crucial in response to microenvironmental cues.
- Cholesterol accumulation significantly impacts macrophage behavior.
Purpose of the Study:
- To review the role of macrophage phenotypes in atherogenesis.
- To investigate the impact of cholesterol on macrophage phenotype.
- To identify potential therapeutic targets for anti-atherogenic immunocorrectors.
Main Methods:
- Analysis of M1 and M2 macrophage distribution in atherosclerotic lesions.
- Transcriptome analysis of cholesterol-loaded macrophages.
- Testing anti-atherogenic drugs on a primary macrophage model.
Main Results:
- Cholesterol loading alters macrophage gene expression, particularly immune-related genes.
- Interaction with modified LDL increases expression of TNF-α and CCL18.
- Macrophage activation profiles show potential for immunocorrection.
Conclusions:
- Macrophage phenotype plasticity is a key factor in atherogenesis.
- Targeting macrophage activation pathways offers a promising strategy for novel anti-atherogenic therapies.
- Tested drugs show potential as immunocorrectors in a macrophage-based model.

