Deficiency of CCAAT/enhancer binding protein-epsilon reduces atherosclerotic lesions in LDLR-/- mice

Area of Science:

• Immunology
• Molecular Biology
• Cardiovascular Research

Background:

• CCAAT/enhancer binding proteins (C/EBPs) are transcription factors crucial for hematopoietic cell development and inflammatory responses.
• C/EBPε is specifically expressed in myeloid cells, including monocytes and macrophages, which are key players in atherosclerosis.
• Atherosclerosis is an inflammatory vascular disease involving monocytes/macrophages and lipid metabolism.

Purpose of the Study:

• To investigate the role of C/EBPε in the context of atherosclerosis using a mouse model.
• To determine how the absence of C/EBPε affects lipid metabolism and atherogenesis in low-density lipoprotein receptor-deficient mice.

Main Methods:

• Generated and analyzed Ldlr and Cebpe double-knockout (llee) mice fed a high-cholesterol diet (HCD).
• Compared atherogenic phenotypes, macrophage lipid uptake, and phagokinetic motility between llee and Ldlr single-deficient (llEE) mice.
• Assessed alterations in lipid metabolism, atheroma formation, obesity, and gene expression (FABP4) in peritoneal macrophages.

Main Results:

• Macrophages from llee mice exhibited reduced lipid uptake and impaired motility compared to llEE mice.
• llee mice showed altered lipid metabolism, reduced atheroma, and decreased obesity, particularly in males.
• Male llee mice displayed reduced mRNA expression of fatty acid binding protein 4 (FABP4) in peritoneal macrophages.

Conclusions:

• Myeloid-specific C/EBPε plays a significant role in systemic lipid metabolism and the development of atherosclerosis.
• Targeting or silencing C/EBPε could potentially reduce atherosclerosis progression and associated lipid dysregulation.