Abstract Body: Introduction/Background
Atherosclerosis-related cardiovascular diseases are the leading cause of morbidity and mortality worldwide. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, Cc1) plays a dual role in vascular biology, supporting early vascular development while fostering chronic inflammation in aging vasculature.

Research Question/Hypothesis
Given the pro-inflammatory role of CEACAM1 in vascular aging, we hypothesized that CEACAM1 contributes to the progression of atherosclerosis. We therefore investigated its impact on atherosclerotic plaque development.

Goals/Aims
This study aimed to define the role of CEACAM1 in atherogenesis using in vivo and in vitro models.

Methods/Approach
Atherosclerotic plaque burden was analyzed in Ldlr^-/- and Ldlr^-/-/Cc1^-/- mice fed a high-fat diet. RNA sequencing of aortic arches was performed to identify differentially regulated signaling pathways. In vitro WT and Cc1^-/- EA.hy926 endothelial cells were analyzed for TNF-α/NF-κB activation, adhesion molecule expression, monocyte adhesion, endothelial permeability and LDL transcytosis.

Results/Data
Ldlr^-/-/Cc1^-/- mice exhibited a more than 50% reduction in atherosclerotic plaque size compared to Ldlr^-/- controls. RNA sequencing revealed that CEACAM1 deficiency led to downregulation of TNF-α/NF-κB signaling, reduced adhesion molecule expression and impaired LDL uptake. Accordingly, in vitro Cc1^-/- endothelial cells showed attenuated TNF-α/NF-κB activation, decreased monocyte adhesion and reduced LDL transcytosis compared to WT controls.

Conclusion
CEACAM1 emerges as a key regulator of atherosclerotic plaque progression by amplifying pro-inflammatory and lipid transport pathways. Therefore, CEACAM1 represents a potential therapeutic target to mitigate atherosclerosis-related cardiovascular complications.