Integrative Analysis of Lactylation-Associated Features in Abdominal Aortic Aneurysm and Its Immune Microenvironment Utilizing scRNA-seq and Bulk RNA Sequencing

Abstract

Background: Abdominal aortic aneurysm (AAA) is a vascular disease strongly associated with immune dysregulation and metabolic disturbances. Although lactate metabolism and its associated process, lactylation, have been implicated in various diseases, their specific role in AAA pathogenesis remains poorly understood.

Methods and Results: In this study, we used a multi-faceted approach, integrating single-cell and bulk RNA data analyses, with the objective of elucidating the interrelationship between lactylation and immune response in AAA patients. The result revealed significant heterogeneity in lactylation levels across different immune cell types. Cells with higher lactylation activity exhibited markedly elevated immune response scores. Differential expression and correlation analyses identified 65 lactylation-associated genes, which were further evaluated in the bulk RNA sequencing data to assess their relationship with the immune microenvironment in patients with AAA. Using 113 combinations of machine-learning algorithms, we identified 8 lactylation-related hub genes. The immune infiltration analysis demonstrated that these genes were linked to a multitude of immune cells. The animal experiments corroborated that Tnfsf8, Hist1 h2ag, Cd79b, Cd69, and Bank1 were upregulated in the AAA group, while Rpl36a and Rps29 were downregulated in the AAA group.

Conclusions: This study highlighted a potentially critical link between lactylation and immune dysregulation in AAA, thereby advancing our comprehension of the function of lactylation in AAA.