Apolipoprotein E derived from CD11c⁺ cells ameliorates atherosclerosis.

Area of Science:

• Immunology
• Cardiovascular Biology
• Lipid Metabolism

Background:

• Atherosclerosis research often utilizes apolipoprotein E-deficient (ApoE-/-) mice to study lipid homeostasis.
• The specific contribution of antigen-presenting cells (APCs) to lipid metabolism and atherosclerosis remains incompletely understood.

Purpose of the Study:

• To investigate the role of CD11c+ cells, a subset of APCs, in lipid homeostasis and atherosclerosis.
• To quantify the contribution of CD11c+ cells to apolipoprotein E (ApoE) production.
• To determine the impact of CD11c+ cell-specific ApoE deletion on atherosclerotic plaque development and inflammation.

Main Methods:

• Utilized LacZ reporter mice to identify CD11c+ cell distribution in the aorta of ApoE-/- mice.
• Employed systemic long-term depletion of CD11c+ cells in ApoE-/- mice.
• Generated CD11c-cre+ApoEfl/fl and Albumin-cre+ApoEfl/fl mice for cell-specific ApoE deletion.
• Assessed serum ApoE levels, atherosclerotic plaque burden, and inflammatory markers (IL-1β).

Main Results:

• CD11c+ cells were found to be enriched in the aortae of ApoE-/- mice.
• Depletion of CD11c+ cells led to increased plaque formation and reduced serum ApoE levels.
• Approximately 25% of serum ApoE was derived from CD11c+ cells, with liver contributing about 70%.
• Cell-specific deletion of ApoE in CD11c+ cells increased atherosclerotic plaque burden and IL-1β serum levels.
• Exposure to acetylated LDL (acLDL) promoted cholesterol efflux from CD11c+ cells.

Conclusions:

• CD11c+ cells are a significant source of ApoE, contributing approximately 25% of its systemic levels.
• CD11c+ cells play a protective role in atherosclerosis by secreting ApoE.
• Targeting CD11c+ cell-derived ApoE represents a potential therapeutic strategy for managing atherosclerosis.