Siglec-E retards atherosclerosis by inhibiting CD36-mediated foam cell formation

Area of Science:

• Immunology
• Cardiovascular Biology
• Cell Biology

Background:

• Atherosclerosis involves foam cell accumulation in the arterial intima.
• Siglec-E, expressed on myeloid cells, typically signals inhibition upon binding sialic acid ligands.
• The role of Siglec-E in macrophage foam cell formation and atherosclerosis was unclear.

Purpose of the Study:

• To investigate the impact of Siglec-E on atherosclerosis development and foam cell formation.
• To elucidate the molecular mechanisms by which Siglec-E influences macrophage lipid uptake.

Main Methods:

• Utilized ApoE-deficient and double-deficient mice on a high-fat diet.
• Assessed atherosclerosis severity and lipid profiles.
• Examined modified LDL uptake and foam cell formation in macrophages in vitro.
• Identified Siglec-E interacting proteins using proximity labeling and proteomics.

Main Results:

• Siglec-E deficiency accelerated atherosclerosis in apoE-/- mice without altering lipid profiles.
• Siglec-E deficiency enhanced modified LDL uptake and foam cell formation in macrophages.
• Identified CD36 as a Siglec-E interacting protein.
• Siglec-E suppresses downstream VAV signaling involved in modified LDL uptake.

Conclusions:

• Siglec-E exhibits a protective role in atherosclerosis.
• Siglec-E functions by interacting with CD36 to inhibit VAV signaling, thereby reducing modified LDL uptake by macrophages.