Neutrophil Elastase is Identified as a Key Regulator of Atherosclerosis and Immune Infiltration by Multi-Omics

Abstract

Neutrophil elastase is a serine protease. The function of neutrophil elastase in vascular targeted therapies in oncology was analyzed by multi-omics analysis. By comparing the neutrophil elastase mRNA levels in atherosclerotic and normal blood vessels, we observed that neutrophil elastase was elevated in atherosclerotic arteries. The neutrophil elastase mRNA expression level in most tumors was lower than in the adjacent tissues, which is not conducive to the clinical prognosis of extensive tumors. Interestingly, neutrophil elastase was highly expressed in colon cancer, head and neck squamous cell carcinoma, and acute myeloid leukemia. There was a positive relationship between neutrophil elastase and the fibroblast immune invasion of various tumors. Furthermore, we obtained 20 hub genes from Cytoscape and verified their mRNA levels in a mouse model of atherosclerosis. The results showed that they were highly expressed in the arteries of mice with high-fat diet-induced atherosclerosis as well as in human atherosclerotic plaques. Neutrophil elastase inhibitors suppressed the ox-low-density-lipoprotein-induced cathepsin G expression. Neutrophil elastase is not only an important risk factor for atherosclerosis but also an important oncogene and a potentially important target in cancer patients with arterial diseases.