Affiliation:
1. 1.Cardiovascular Department, Taihe Hospital, Hubei University of Medicine, 442000, Shiyan, Hubei
2. 2.Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, 442000, Shiyan, Hubei
Abstract
Abstract
Background Atherosclerosis (As) is a serious threat to human health. Although glucose balance, lipid metabolism, inflammation and hypertension have been found to be closely related to AS, it is crucially unclear, whether methyltransferase (METTL) family members are involved in the occurrence and development of AS.Methods The differentially expressed genes of METTLs in AS and normal blood vessels in GSE43292 and GSE100927 databases were analyzed. Random forest screening was used to screen marker genes, and the intersection genes in two databases were selected, while GSE28829/GSE41571 and clinical tissue samples were used for verification. The databases were further used to analyze the tissue and cell localization of marker genes and their correlation with lipid metabolism and immune cell infiltration.Results There were 7 and 17 differentially expressed METTL genes in GSE43292 and GSE100927 databases, respectively. 7 and 10 AS risk genes were selected by random forest screening. METTL7B and METTL5 were verified as the intersection marker genes using GSE28829, GSE41571 database and clinical AS samples. Compared with the control group, the expression of METTL7B in advanced AS, AS rupture plaque and clinical heavy load plaque tissue significantly increased, and the ROC curve analysis showed that the AUC of METTL7B in GSE28829 and GSE41571 was greater than 0.9. In addition, it was found that METTL7B was significantly correlated with lipid metabolism-related genes, and METTL7B could promote the formation of lipid droplets. METTL7B was positively correlated with immune cell infiltration and macrophage-mediated efferocytosis. Drugs such as FAD, Pralatrexate and Indinavir can act on METTL7B. This study reveals a new mechanism for the occurrence and development of AS thereby providing a potential target for the treatment of AS.Conclusion METTL7B can be used as a predictor and therapeutic target for AS.
Publisher
Research Square Platform LLC
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