Abstract
Immune infiltration plays an important role in the course of abdominal aortic aneurysm (AAA) development, and copper death (cuproptosis) is a new type of programmed cell death recently discovered. Currently, there are no studies on the role of cuproptosis regulating immune infiltration in AAA. We extracted a published GEO dataset (GSE57691), with 49 AAA and 10 control transcriptome sequencing samples. Then, we analyzed the difference of cuproptosis related genes (CRGs) expression between AAA and normal groups. LIPT1, FDX1 and CDKN2A were upregulated in AAA samples (P < 0.05). Subsequently, we analyzed the difference of immune infiltrate cells between the AAA and normal samples. Compared to the normal group, Dendritic cells, Mast activated cells, Monocytes, M0 macrophages, neutrophils, Plasma cells, CD4-naive T cells, follicular-helper T cells and Treg cells were upregulated in the AAA group, while M1 and M2 macrophages, CD4-memory T cells and gamma delta T cells were downregulated. AAA samples were then classified into two subtypes according to the expression profiles of CRGs, the immunological characteristics and function had significant differences between subtypes. Furthermore, we mined 20 hub genes by using Weighted Gene Co-expression Network Analysis (WGCNA) to construct a co-expression network. Three drugs were identified that interacting with eight hub genes based on the gene-drug interaction database. We finally verified the mRNA differences of the CRGs in the aorta of AAA and healthy mice in vitro. LIPT1, CDKN2A and FDX1 may play a role in regulating the development of AAA through immune infiltration. Eight NDUF subunits, including NDUFA1, NDUFA4, and NDUFB1, may also play an important role in this process. In addition, Metformin, ME-344 and NV-128 may be therapeutic agents for AAA by regulating the cuproptosis.