Cholesterol-load evokes robust calcium response in macrophages: An early event toward cholesterol-induced macrophage death

Hirotaka Fujita, Chihiro Adachi, Takafumi Inoue*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Macrophages in atherosclerotic lesions accumulate large amounts of unesterified cholesterol. Excess cholesterol load leads to cell death of macrophages, which is associated with the progression of atherosclerotic lesions. Calcium depletion in the endoplasmic reticulum (ER) and subsequent pro-apoptotic aberrant calcium signaling are key events in cholesterol-induced macrophage death. Although these concepts imply cytoplasmic calcium events in cholesterol-loaded macrophages, the mechanisms linking cholesterol accumulation to cytoplasmic calcium response have been poorly investigated. Based on our previous finding that extracellularly applied cholesterol evoked robust calcium oscillations in astrocytes, a type of glial cells in the brain, we hypothesized that cholesterol accumulation in macrophages triggers cytoplasmic calcium elevation. Here, we showed that cholesterol application induces calcium transients in THP-1-derived and peritoneal macrophages. Inhibition of inositol 1,4,5-trisphosphate receptors (IP3Rs) and L-type calcium channels (LTCCs) prevented cholesterol-induced calcium transients and ameliorated cholesterol-induced macrophage death. These results suggest that cholesterol-induced calcium transients through IP3Rs and LTCCs are crucial mechanisms underlying cholesterol-induced cell death of macrophages.

Original languageEnglish
Article number102754
JournalCell Calcium
Volume113
DOIs
Publication statusPublished - 2023 Jul

Keywords

  • Calcium
  • Cell death
  • Cholesterol
  • Inositol 1,4,5-trisphosphate receptor
  • L-type calcium channel
  • Macrophage

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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