Alternative macrophages in atherosclerosis: not always protective!

Area of Science:

• Vascular Biology
• Immunology
• Cardiovascular Disease

Background:

• Atherosclerosis involves chronic vascular inflammation initiated by cholesterol deposition.
• Plaque progression leads to hypoxia, promoting angiogenesis and vessel leakage, contributing to plaque instability and hemorrhage.
• Macrophages with diverse phenotypes, including anti-inflammatory CD163+ subtypes, are found in atherosclerotic lesions, but their specific role remains unclear.

Purpose of the Study:

• To investigate the role of CD163+ macrophages in atherogenesis.
• To elucidate the mechanisms by which CD163+ macrophages influence plaque progression, angiogenesis, and inflammation.

Main Methods:

• Analysis of human and mouse atherosclerotic lesions.
• Investigation of macrophage phenotypes, particularly CD163+ macrophages.
• Examination of mechanisms involving hemoglobin, haptoglobin, CD163, HIF1α, and VEGF.

Main Results:

• CD163+ macrophages were found to promote angiogenesis and vessel permeability in atherosclerotic lesions.
• These macrophages enhance leukocyte infiltration into the plaque.
• A mechanism involving hemoglobin:haptoglobin/CD163/HIF1α-mediated VEGF induction was identified as responsible for these pro-atherogenic effects.

Conclusions:

• CD163+ macrophages possess pro-atherogenic properties, contrary to previous assumptions of a beneficial role.
• These macrophages contribute to atherosclerosis by promoting angiogenesis, vascular permeability, and inflammation.
• Targeting CD163+ macrophage pathways may offer novel therapeutic strategies for atherosclerosis.