Our objectives were to characterize (1) whether the levels of O-GlcNAcylated desmin are regulated in cardiomyocyte by inhibition or activation of O-GlcNAcylation in in vitro and ex vivo cardiac models of HF and; (2) whether modulation of O-GlcNAcylation impacts the phosphorylation levels of desmin with the aim to decrease the phosphorylation levels of desmin and the formation of desmin aggregates following HF development. The gene discussed is DES; the disease is hydrops fetalis.