RNA methylation patterns, immune characteristics, and autophagy- related mechanisms mediated by m6A regulatory factors in venous thromboembolism

Abstract

Abstract Recent studies have found a link between deep vein thrombosis and inflammatory reactions. N6-methyladenosine (m6A), a crucial element in immunological regulation, is believed to contribute to the pathophysiology of venous thromboembolism (VTE). However, how the m6A-modified immune microenvironment is involved in VTE remains unclear. In the present study, we identified a relationship between VTE and the expression of several m6A regulatory elements by analyzing peripheral blood samples from 177 patients with VTE and 88 healthy controls in a public database. We used machine learning to identify essential genes and constructed a diagnostic model for VTE using multivariate logistic regression. Unsupervised cluster analysis revealed a marked difference between m6A modification patterns in terms of immune cell infiltration, inflammatory reactivity, and autophagy. We identified two m6A-related autophagy genes (i.e., CHMP2B and SIRT1) and the crucial m6A regulator YTHDF3 using bioinformatics. We also examined two potential mechanisms through which YTHDF3 may affect VTE. Altered methylation modification techniques on m6A may enhance the inflammatory reaction during the thrombosis phase and contribute to the occurrence of VTE. Increasing SIRT1–FOXO1 autophagy pathway activity may increase macrophage proliferation, inflammatory response, and VTE risk. This study established an intimate relationship between m6A alteration, the immunological milieu of VTE, and autophagy, providing further insights into the pathogenic process and development of innovative VTE therapeutics.