Background: O-linked N-acyl-glycosylation may regulate protein function by competing with phosphorylation of serine residues. Availability of substrate for this process is regulated, in part, by N-Acyl-D-glucosamine 2-epimerase (NAGE), which interconverts N-acetyl-glucosamine (GlcNAc) and N-acetylmannosamine (ManNAc). NAGE is also a putative renin-binding protein. This study tested the hypothesis that NAGE is present in the human heart and that NAGE expression is increased in the failing human heart.
Methods and results: Ribonuclease protection assays (RPAs) demonstrated increased NAGE gene expression in failing hearts from subjects with idiopathic dilated and ischemic cardiomyopathies compared with nonfailing hearts. In situ reverse transcriptase-polymerase chain reaction, using primers designed to localize NAGE mRNA, demonstrated that, in nonfailing hearts, NAGE gene expression was restricted to endothelial cells and not detectable in cardiac myocytes. However, in failing human hearts NAGE gene expression was selectively activated in cardiac myocytes, but not endothelial cells. Immunohistochemistry confirmed that the pattern of NAGE protein expression corresponded to the pattern of gene expression.
Conclusions: NAGE gene and protein expression were selectively activated in left ventricular myocytes from end-stage failing human hearts.