Annexin A8 deficiency delays atherosclerosis progression

Area of Science:

• Cardiovascular Biology
• Inflammation and Immunology
• Molecular Medicine

Background:

• Atherosclerosis is a chronic inflammatory disease driven by lipid and leukocyte accumulation in arterial walls.
• Identifying novel molecular players is crucial for understanding and treating atherosclerosis progression.

Purpose of the Study:

• To investigate the role of AnxA8 in atherosclerosis using a mouse model.
• To determine if AnxA8 expression in endothelial cells influences atherosclerotic plaque development.

Main Methods:

• RNA-sequencing of aortas from apolipoprotein E knockout (ApoE-/-) and wild-type mice.
• Generation of ApoE-/- mice lacking AnxA8 systemically or specifically in bone marrow-derived cells.
• Endothelial-specific AnxA8 silencing in vivo and in vitro functional assays in cultured cells.

Main Results:

• AnxA8 was significantly upregulated in atherosclerotic aortas of ApoE-/- mice and human plaques.
• Germline AnxA8 deficiency reduced atherosclerotic burden, plaque size, lipid content, and inflammation.
• Endothelial AnxA8 promoted ox-LDL-induced expression of adhesion molecules, reducing leukocyte and platelet adhesion.

Conclusions:

• AnxA8 promotes atherosclerosis by modulating endothelial-leukocyte interactions.
• Targeting AnxA8 in endothelial cells may represent a therapeutic strategy to delay atherosclerotic plaque progression.