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Updated: Jan 3, 2026
An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization
Published on: June 12, 2013
Diversity of macrophage phenotypes and responses in atherosclerosis
Hiroyuki Jinnouchi1, Liang Guo1, Atsushi Sakamoto1
1CVPath Institute, 19 Firstfield Road, Gaithersburg, MD, 20878, USA.
Abstract:
The presence of macrophages within the plaque is a defining hallmark of atherosclerosis. Macrophages are exposed to various microenvironments such as oxidized lipids and cytokines which effect their phenotypic differentiation and activation. Classically, macrophages have been divided into two groups: M1 and M2 macrophages induced by T-helper 1 and T-helper 2 cytokines, respectively. However, for a decade, greater phenotypic heterogeneity and plasticity of these cells have since been reported in various models. In addition to M1 and M2 macrophage phenotypes, the concept of additional macrophage phenotypes such as M (Hb), Mox, and M4 has emerged. Understanding the mechanisms and functions of distinct phenotype of macrophages can lead to determination of their potential role in atherosclerotic plaque pathogenesis. However, there are still many unresolved controversies regarding their phenotype and function with respect to atherosclerosis. Here, we summarize and focus on the differential subtypes of macrophages in atherosclerotic plaques and their differing functional roles based upon microenvironments such as lipid, intraplaque hemorrhage, and plaque regression.
Insights
Macrophages in atherosclerosis exhibit diverse phenotypes beyond M1/M2, including M(Hb), Mox, and M4. Understanding these macrophage subtypes and their roles in plaque microenvironments is crucial for atherosclerosis research.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Biology
Background:
- Macrophages are key players in atherosclerosis.
- Macrophage phenotypes are influenced by plaque microenvironments.
- Classical M1/M2 classification is insufficient to describe macrophage heterogeneity.
Purpose of the Study:
- To review and focus on distinct macrophage subtypes in atherosclerotic plaques.
- To elucidate the functional roles of these macrophage phenotypes.
- To explore the impact of microenvironments like lipids, intraplaque hemorrhage, and plaque regression on macrophage function.
Main Methods:
- Literature review and synthesis of existing research on macrophage phenotypes in atherosclerosis.
- Focus on differential subtypes beyond M1/M2, including M(Hb), Mox, and M4.
- Analysis of functional roles based on specific plaque microenvironmental factors.
Main Results:
- Macrophages display significant phenotypic heterogeneity and plasticity in atherosclerosis.
- Emerging macrophage phenotypes (M(Hb), Mox, M4) play roles distinct from classical M1/M2.
- Microenvironmental factors critically shape macrophage function within atherosclerotic plaques.
Conclusions:
- Understanding diverse macrophage phenotypes is essential for comprehending atherosclerosis pathogenesis.
- Further research is needed to resolve controversies regarding specific macrophage subtype functions in atherosclerosis.
- Targeting specific macrophage phenotypes may offer therapeutic potential for atherosclerosis.
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