Conversion of M1 Macrophages to Foam Cells: Transcriptome Differences Determined by Sex

Area of Science:

• Immunology
• Cardiovascular Biology
• Genomics

Background:

• M1 macrophages, crucial in inflammation, become foam cells when exposed to low-density lipoproteins (LDL).
• Atherosclerotic plaques show more advanced lesions and infiltration in males.
• Sex-based differences in macrophage responses to LDL are critical for understanding atherosclerosis.

Purpose of the Study:

• To investigate sex-specific transcriptomic changes in M1 macrophages during LDL internalization.
• To identify differential gene expression patterns between male and female M1 macrophages in response to LDL.

Main Methods:

• Isolation of monocytes from peripheral blood mononuclear cells (PBMCs) of healthy males and females.
• Stimulation of CD14+ cells with LDL (10 µg/mL) to induce M1 macrophage phenotype.
• Transcriptome analysis using Clariom D platform array during LDL internalization.

Main Results:

• Male M1 macrophages exhibited 43% of transcripts influenced by the Y chromosome in response to LDL.
• Shared transcripts between sexes primarily involved non-coding elements related to oxidative stress and endothelial damage.
• Significant differences in gene expression profiles were observed between male and female M1 macrophages.

Conclusions:

• Male monocyte-derived M1 macrophages demonstrate a more pronounced pro-inflammatory gene expression profile during LDL internalization.
• Female M1 macrophages present a greater number of markers associated with cellular damage.
• These findings highlight distinct sex-specific immune responses in the context of LDL-induced inflammation and atherosclerosis.