Screening of potential regulatory genes in carotid atherosclerosis vascular immune microenvironment

Background: Immune microenvironment is one of the essential characteristics of carotid atherosclerosis (CAS), which cannot be reversed by drug therapy alone. Thus, there is a pressing need to develop novel immunoregulatory strategies to delay this pathological process that drives cardiovascular-related diseases. This study aimed to detect changes in the immune microenvironment of vascular tissues at various stages of carotid atherosclerosis, as well as cluster and stratify vascular tissue samples based on the infiltration levels of immune cell subtypes to distinguish immune phenotypes and identify potential hub genes regulating the immune microenvironment of carotid atherosclerosis. Materials and methods: RNA sequencing datasets for CAS vascular tissue and healthy vascular tissue (GSE43292 and GSE28829) were downloaded from the Gene Expression Omnibus (GEO) database. To begin, the immune cell subtype infiltration level of all samples in both GSE43292 and GSE28829 cohorts was assessed using the ssGSEA algorithm. Following this, consensus clustering was performed to stratify CAS samples into different clusters. Finally, hub genes were identified using the maximum neighborhood component algorithm based on the construction of interaction networks, and their diagnostic efficiency was evaluated. Results: Compared to the controls, a higher number of immune cell subtypes were enriched in CAS samples with higher immune scores in the GSE43292 cohort. Advanced CAS was characterized by high immune cell infiltration, whereas early CAS was characterized by low immune cell infiltration in the GSE28829 cohort. Moreover, CAS progression may be related to the immune response pathway. Biological processes associated with muscle cell development may impede the progression of CAS. Finally, the hub genes PTPRC, ACTN2, ACTC1, LDB3, MYOZ2, and TPM2 had satisfactory efficacy in the diagnosis and prediction of high and low immune cell infiltration in CAS and distinguishing between early and advanced CAS samples. Conclusion: The enrichment of immune cells in vascular tissues is a primary factor driving pathological changes in CAS. Additionally, CAS progression may be related to the immune response pathway. Biological processes linked to muscle cell development may delay the progression of CAS. PTPRC, ACTN2, ACTC1, LDB3, MYOZ2, and TPM2 may regulate the immune microenvironment of CAS and participate in the occurrence and progression of the disease.