OBJECTIVE

To explore differentially expressed endoplasmic reticulum stress-associated genes (ERSAGs) in aortic dissection (AD) and their correlations with immune cell infiltration to identify new therapeutic targets for AD.

METHODS

Two AD mRNA expression datasets (GSE190635 and GSE98770) were downloaded from GEO database for analysis of differentially expressed genes between the aorta of AD patients and normal aorta using R software. ERSAGs dataset was downloaded from GeneCards website, and GeneMANIA database was used to analyze the protein-protein interaction network of the differentially expressed ERSAGs and the proteins interacting with these genes. Based on GSE98770 dataset we analyzed the distributions of 22 immune cells within the aortic wall of AD patients using CIBERSORT package of R software. Surgical aortic wall specimens were obtained from 10 AD patients and 10 non-AD patients for detecting mRNA expression using qRTPCR, and the upstream transcriptional factors, miRNAs, and chemicals targeting were analyzed using the TRRUST database and NetworkAnalyst database.

RESULTS

Bioinformatic analysis suggested significant differential expression of in AD, which interacted with 20 proteins involved in pattern recognition receptor signaling pathway, positive regulation of DNA-binding transcription factor activity, myeloid leukocyte migration, leukocyte migration, and regulation of the I-κB kinase/NF-κB signaling. In AD, AGER expression level was positively correlated with Treg cell abundance (=0.59, < 0.05). The results of qRT-PCR demonstrated significantly lower expression of mRNA in AD than in non-AD patients (1.00±0.30 1.76±0.68, < 0.05). ROC curve analysis showed that at the cut-off value of 1.335, AGER had an AUC of 0.86 (95% : 0.67-1.00, = 0.0073) for predicting AD. Three transcriptional factors, 3 miRNAs, and 27 chemicals were predicted in the AGER regulatory network.

CONCLUSION

is lowly expressed in the aorta of AD patients and may influence the occurrence of AD through Treg cells.