O-GlcNAcylation And The Yes Associated Protein - New Paradigm In Heart Failure?

• Published in: Journal of cardiac failure 2024-01, Vol.30 (1), p.290-290
• Main Author: Umapathi, Priya
• Format: Article
• Language: English
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2023.10.411

Heart failure is strongly tied to cardiac stressors and interlinked with increased levels of O-beta-N-Acetylglucosamine modified proteins in the heart. O-GlcNAc levels are determined by the net activity of two enzymes, OGT (O-GlcNAc Transferase) and OGA (O-GlcNAcase). We have previously shown mouse models of myocardial OGT overexpression (OGT TG) develop heart failure. Mouse models of myocardial OGA overexpression (OGA TG) have decreased OGN and interbreeding OGT TG with OGA TG normalizes O-GlcNAcylation levels and rescues heart failure. The heart utilizes multiple adaptive mechanisms to maintain cardiac function and our data suggest a connection between O-GlcNAcylation and the Yes Associated Protein, a known mediator of cardiac hypertrophy. Evaluate the effects of O-GlcNAcylation on Yes Associated Protein activity in the heart. We quantified levels of activated YAP protein and gene expression in hearts from WT, OGT and OGA hearts. Utilizing a YAP transcriptional reporter we studied the effects of O-GlcNAc levels on YAP in cardiac cells. Our preliminary data found increased, activated (nuclear) YAP in OGT TG and increased YAP reporter activity in the setting of increased O-GlcNAcylation in cardiac myocytes. These data suggest O-GlcNAc influences the behavior of YAP in the heart and may represent a novel, modifiable axis in the development of cardiac hypertrophy and heart failure.