Macrophage PIM1 Drives Atherosclerosis by Enhancing Foam Cell Formation Via CD36

Area of Science:

• Immunology
• Cell Biology
• Cardiovascular Research

Background:

• Atherosclerosis involves macrophage (Mφ) scavenger receptor CD36 and fatty plaque buildup.
• PIM1 kinase's role in Mφ lipid handling and atherogenesis remains unclear.
• This study investigates PIM1's regulation of CD36 in Mφs during foam cell formation and atherosclerosis.

Purpose of the Study:

• To determine the role of PIM1 in regulating CD36 expression and function in macrophages.
• To investigate PIM1's impact on lipid handling and foam cell formation in macrophages.
• To assess the effect of Mφ-specific PIM1 deficiency on atherosclerosis progression in vivo.

Main Methods:

• In vitro studies using PIM1-deficient and wild-type murine macrophages treated with oxidized LDL (oxLDL).
• In vivo studies using Mφ-specific PIM1-deficient and control mice fed a high-fat diet.
• Analysis of CD36, PIM1, oxLDL binding/uptake, foam cell formation, and atherosclerotic plaque size.

Main Results:

• PIM1 deletion in Mφs significantly reduced CD36 expression, oxLDL uptake, and foam cell formation.
• PIM1 deficiency downregulated PPARγ signaling, which was restored by a PPARγ agonist.
• Mφ-specific PIM1 deficiency markedly reduced atherosclerotic plaque formation in mice.

Conclusions:

• PIM1 is a key regulator of CD36 expression and activity in Mφs via PPARγ.
• The PIM1-CD36 pathway promotes Mφ lipid accumulation and foam cell formation.
• Targeting the PIM1/PPARγ/CD36 axis presents a potential therapeutic strategy for atherosclerosis.