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Macropinocytosis promotes foam cell formation and atherosclerosis

Nature Reviews Cardiology volume 19, page 781 (2022)Cite this article

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Foam cell accumulation has a central role in the development and progression of atherosclerosis, and internalization of LDL through scavenger receptors (SR) is the most widely accepted mechanism for macrophage foam cell formation. However, a new study has identified an SR-independent mechanism of atherosclerosis development by showing that LDL uptake through macropinocytosis — a type of endocytosis involving nonspecific uptake of extracellular fluid and solutes — contributes to macrophage foam cell formation and atherosclerosis development. Furthermore, the findings suggests a potential new therapeutic approach. “Repurposing an FDA-approved drug that inhibits macropinocytosis inhibited atherosclerosis development in mice,” highlights lead investigator Gábor Csányi.

By contrast, stimulation of macrophage macropinocytosis promoted foam cell formation and increased LDL uptake by human macrophages in vitro and in wild-type and SR-knockout (Cd36−/−Sra−/−) mice. Finally, analyses involving serial section high-resolution imaging, LDL immunolabelling and 3D reconstruction of subendothelial foam cells provided visual evidence of lipid macropinocytosis in human and mouse atherosclerotic arteries.

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References

Original article

  • Lin, H.-P. et al. Receptor-independent fluid-phase macropinocytosis promotes arterial foam cell formation and atherosclerosis. Sci. Transl. Med. 14, eadd2376 (2022)

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Irene Fernández-Ruiz

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  1. Irene Fernández-Ruiz
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Correspondence to Irene Fernández-Ruiz.

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Fernández-Ruiz, I. Macropinocytosis promotes foam cell formation and atherosclerosis. Nat Rev Cardiol 19, 781 (2022). https://doi.org/10.1038/s41569-022-00798-3

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  • DOI: https://doi.org/10.1038/s41569-022-00798-3

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