Mast cell St8sia1-GD3 axis as a glyco-epigenetic checkpoint driving maladaptive cardiac remodeling [RNA-seq]

Glycoconjugates, which are crucial for signal transduction and extracellular matrix integrity, represent an underexploited therapeutic avenue. This study sought to define the role of glycoconjugate-metabolizing enzymes at the immune-cardiac interface and evaluate their translational potential.

We performed integrative analyses of bulk and single-cell RNA sequencing data from failing human and mouse hearts. Employing mouse models of pressure overload (transverse aortic constriction, TAC) and ischemia-reperfusion (IR), we utilized global and mast cell (MC)-specific gene deletion, bone-marrow chimeras, and pharmacologic neutralization. Mechanistic insights were gained through multi-omics profiling, including RNA-seq, ATAC-seq, and CUT&Tag.