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

Area of Science:

• Cardiovascular Biology
• Cellular Physiology
• Immunology

Background:

• Macrophages in atherosclerotic lesions accumulate excess unesterified cholesterol.
• This cholesterol overload induces macrophage death, contributing to atherosclerotic lesion progression.
• Aberrant calcium signaling, particularly endoplasmic reticulum calcium depletion, is implicated in cholesterol-induced macrophage death.

Purpose of the Study:

• To investigate the mechanisms linking cholesterol accumulation to cytoplasmic calcium elevation in macrophages.
• To test the hypothesis that cholesterol accumulation triggers cytoplasmic calcium increase in macrophages.
• To explore the role of calcium signaling pathways in cholesterol-induced macrophage death.

Main Methods:

• Cholesterol application to THP-1-derived and peritoneal macrophages.
• Measurement of intracellular calcium transients.
• Pharmacological inhibition of inositol 1,4,5-trisphosphate receptors (IP3Rs) and L-type calcium channels (LTCCs).

Main Results:

• Cholesterol application induced significant calcium transients in macrophages.
• Inhibition of IP3Rs and LTCCs effectively prevented cholesterol-induced calcium transients.
• Blocking these calcium channels ameliorated cholesterol-induced macrophage death.

Conclusions:

• Cholesterol accumulation in macrophages triggers cytoplasmic calcium elevation via IP3Rs and LTCCs.
• These cholesterol-induced calcium transients are critical mediators of macrophage cell death.
• Targeting these calcium pathways may offer therapeutic strategies for atherosclerosis.