The roles of O-linked β-N-acetylglucosamine in cardiovascular physiology and disease

Zachara NE. The roles of O-linked beta-N-acetylglucosamine in cardiovascular physiology and disease. Am J Physiol Heart Circ Physiol 302: H1905-H1918, 2012. First published January 27, 2012; doi: 10.1152/ajpheart.00445.2011.-More than 1,000 proteins of the nucleus, cytoplasm, and mitochondria are dynamically modified by O-linked beta-N-acetylglucosamine (O-GlcNAc), an essential post-translational modification of metazoans. O-GlcNAc, which modifies Ser/Thr residues, is thought to regulate protein function in a manner analogous to protein phosphorylation and, on a subset of proteins, appears to have a reciprocal relationship with phosphorylation. Like phosphorylation, O-GlcNAc levels change dynamically in response to numerous signals including hyperglycemia and cellular injury. Recent data suggests that O-GlcNAc appears to be a key regulator of the cellular stress response, the augmentation of which is protective in models of acute vascular injury, trauma hemorrhage, and ischemia-reperfusion injury. In contrast to these studies, O-GlcNAc has also been implicated in the development of hypertension and type II diabetes, leading to vascular and cardiac dysfunction. Here we summarize the current understanding of the roles of O-GlcNAc in the heart and vasculature.