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Published on: December 7, 2013
Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis
Yuri V Bobryshev1, Ekaterina A Ivanova2, Dimitry A Chistiakov3
1Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia; Faculty of Medicine, School of Medical Sciences, University of New South Wales, Kensington, Sydney, NSW 2052, Australia; School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
Insights
Macrophages are key players in atherosclerosis, a chronic inflammatory disease. Targeting these cells offers potential for new anti-atherosclerosis therapies by modulating their inflammatory roles and cholesterol handling.
Area of Science:
- Cardiovascular Biology
- Immunology
- Pathology
Background:
- Atherosclerosis is characterized by chronic inflammation, with macrophages playing dual roles.
- Proinflammatory macrophages accumulate cholesterol and destabilize plaques.
- Anti-inflammatory macrophages aid in plaque stabilization and tissue repair.
Purpose of the Study:
- To review macrophage diversity, activation, and plasticity in atherosclerosis.
- To explore macrophage-based strategies for anti-atherosclerotic therapy.
- To present cellular assays for evaluating anti-atherosclerotic substances.
Main Methods:
- Literature review of macrophage roles in atherosclerosis.
- Analysis of macrophage phenotypes and functions.
- Description of macrophage-based cellular assays.
Main Results:
- Macrophages exhibit diverse phenotypes with distinct roles in plaque development and stability.
- Therapeutic strategies can target monocyte recruitment, proinflammatory macrophages, or anti-inflammatory responses.
- Macrophage plasticity is crucial in the pathogenesis of atherosclerosis.
Conclusions:
- Macrophages are critical targets for anti-atherosclerotic drug development.
- Further research is needed for comprehensive macrophage classification and role definition.
- Macrophage-based assays can evaluate potential therapeutic agents.
Abstract:
Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances.
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