Identification of monocyte-associated pathways participated in the pathogenesis of pulmonary arterial hypertension based on omics-data.

Abstract

Pulmonary arterial hypertension (PAH) is one kind of chronic and uncurable diseases that can cause heart failure. Immune microenvironment plays a significant role in PAH. The aim of this study was to assess the role of immune cell infiltration in the pathogenesis of PAH.Differentially expressed genesbased on microarray data were enriched in several immune-related pathways. To evaluate the immune cell infiltration, based on the microarray data sets in the GEO database, we used both ssGSEA and the CIBERSORT algorithm. Additionally, single-cell RNA sequencing(scRNA-seq) data was used to further explicit the specific role and intercellular communications. Then receiver operating characteristiccurves and least absolute shrinkage and selection operatorwere used to discover and test the potential diagnostic biomarkers for PAH.Both the immune cell infiltration analyses based on the microarray data sets and the cell proportion in scRNA-seq data exhibited a significant downregulation in the infiltration of monocytes in PAH. Then, the intercellular communications showed that the interaction weighs of most immune cells, including monocytes changed between the control and PAH groups, and the ITGAL-ITGB2 and ICAM signaling pathways played critical roles in this process. In addition, ITGAM and ICAM2 displayed good diagnosis values in PAH. This study implicated that the change of monocyte was one of the key immunologic features of PAH. Monocyte-associated ICAM-1 and ITGAL-ITGB2 signaling pathways might be involved in the pathogenesis of PAH.