Dysregulated ApoD Glycosylation Fuels Inflammation-Calcification Coupling in Aortic Valve Disease

Abstract

Calcific aortic valve disease(CAVD)affects more than 5%of individuals over 65 years,yet no pharmacological therapy exists to halt its progression.Inflammation and lipid deposition are known drivers,but the molecular links between these processes remain incompletely defined.Here we show that glycosylation-related enzymes are dysregulated in human calcified valves based on bioinformatics analysis of public datasets(GSE12644).We identified MGAT3,FUT8,and B3GNT2 as key enzymes significantly downregulated in CAVD,with MGAT3 showing a logFC of-1.59(adj.P = 0.0336),FUT8 showing a logFC of-2.25(adj.P = 0.0443),and B3GNT2 showing a logFC of-4.43(adj.P = 0.0336).These enzymes are enriched in N-glycan biosynthesis and inflammatory pathways.Correlation analysis revealed that these enzymes are significantly associated with immune cell infiltration,particularly macrophages.Our findings suggest that dysregulated glycosylation of ApoD may contribute to CAVD pathogenesis through modulating the inflammatory microenvironment,and identify glycosylation enzymes as potential diagnostic biomarkers for this intractable disease.