ABSTRACT NUMBER: ESOC2026A2050 CBS REVERSES ENDOTHELIAL CELL SENESCENCE AND INHIBITS ATHEROSCLEROSIS FORMATION

Abstract Background and aims This study aims to explore the potential mechanisms of Cystathionine β-synthase (CBS)-mediated reversal of cellular senescence and their roles in atherosclerotic plaque formation. Methods We used the CRISPR-SAM system in endothelial cells to screen out reversing senescence-associated genes. Subsequently, CBS was introduced into senescent cell models via adeno-associated virus (AAV)-BI30 to evaluate senescence-related indicators such as senescence, proliferation, autophagy, lysosomal changes, epigenetic alterations, and the secretion of the senescence-associated secretory phenotype (SASP). Finally, ApoE-/- atherosclerotic mice were used, and 1011 AAV-BI30-CBS were administered via tail vein injection, respectively, to observe changes in plaque volume, tissue structure, and the degree of endothelial cell senescence in each group. Results The screening process identified CBS as the lead gene. CBS reversed endothelial cell senescence, promoted proliferation and autophagy, reduced the number of lysosomes, maintain nuclear membrane instability, restored epigenetic changes, and inhibited the secretion of SASP. Additionally, CBS alleviated atherosclerotic plaque formation in ApoE-/- mice and reduced the senescent cell burden in atherosclerotic lesions. Conclusions Our findings indicate that CBS can inhibit the formation of atherosclerosis, and this therapeutic effect is achieved by reversing endothelial cell senescence. This provides a new treatment option for patients with atherosclerosis. Conflict of interest Yilong zhao: nothing to disclose