Macrophage plasticity in experimental atherosclerosis.

Area of Science:

• Immunology
• Cardiovascular Research
• Atherosclerosis Pathogenesis

Background:

• Macrophages (MØ) are key players in atherosclerosis development and progression.
• Understanding MØ phenotype dynamics is crucial for therapeutic strategies.

Purpose of the Study:

• To investigate the phenotype of macrophages associated with atherosclerosis progression in apolipoprotein E (ApoE) knockout (KO) mice.
• To determine if MØ phenotype switching occurs in vivo and if it is driven by cell conversion.

Main Methods:

• Utilized bone marrow-derived MØ for in vitro M1/M2 polarization studies.
• Assessed arginase I (Arg I) and arginase II (Arg II) expression to distinguish M1 and M2 MØ phenotypes.
• Analyzed MØ distribution in atherosclerotic plaques of ApoE KO mice.
• Performed in vitro repolarization experiments to assess MØ plasticity.

Main Results:

• M1 MØ expressed Arg II, while M2 MØ expressed Arg I.
• Early lesions contained M2 MØ, which promoted smooth muscle cell proliferation in vitro.
• M1 MØ became dominant in aged ApoE KO mice, correlating with lesion progression.
• In vitro experiments demonstrated MØ plasticity, with the ability to revert phenotypes.
• In vivo data suggested M2 to M1 MØ conversion within existing lesions, rather than new M1 MØ recruitment.

Conclusions:

• The M2 to M1 macrophage phenotype switch in atherosclerosis is likely due to conversion of resident cells, not solely recruitment.
• Targeting MØ phenotype to promote an M2 phenotype may represent a viable atheroprotective strategy.