In silico analysis and verification of critical genes related to vascular calcification in multiple diseases

Abstract

AbstractIdentifying a functional molecular therapeutic target of vascular calcification (VC) that will not affect normal osteogenic differentiation is a challenge. To address this aim, we screened the differentially expressed genes (DEGs) in different VC conditions, including endothelial‐osteogenic transition (EOT) (GSE167962), chronic kidney disease (CKD), and atherosclerosis (AS) (GSE159832). KEGG pathways, protein–protein interactions, and hub genes were also analyzed. The intersecting DEGs among the EOT, CKD, and AS groups were verified by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in a DOCA‐salt hypertension mouse model. The phosphoinositide 3‐kinase–protein kinase B signaling pathway, ECM‐receptor interaction, chemokine signaling pathway, and focal adhesion were enriched in EOT and AS‐induced VC. ECM‐receptor interaction, PPAR signaling pathway, apelin signaling pathway, AMPK signaling pathway, adipocytokine signaling pathway, and cholesterol metabolism were enriched in CKD and AS‐induced VC. C4b, Cebpa, Lyz2, and Spp1 were also upregulated in EOT, CKD, AS, and hypertension. This study identified promising molecular targets for VC therapy.