O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease

O-GlcNAcylation is a ubiquitous post-translational modification regulated by O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in response to environmental and genetic alterations. It occurs in the nucleus, mitochondrion, and cytoplasm and is implicated in cardiovascular disease (CVD) development. O-GlcNAcylation modulates diverse cellular processes, including metabolic pathways, signaling networks, and transcriptional programs. Acute increase in O-GlcNAcylation serves as an adaptive response that preserves cardiac function, whereas chronic elevation leads to persistent metabolic dysregulation and promotes pathological cardiac remodeling. In this review, we provide a comprehensive overview of the role of O-GlcNAcylation across diverse disease contexts. We also summarize the current understanding of its complex interplay with CVD, including the underlying mechanisms. Finally, we highlight existing knowledge gaps and discuss the therapeutic potential of targeting O-GlcNAcylation in various cardiovascular events, emphasizing key priorities for future research.