The Role of O-GlcNAc Transferase in Regulating the Gene Transcription of Developing and Failing Hearts

ABSTRACT 

Heart failure treatment currently centers on symptom management, primarily through reductions in systemic blood pressure and fluid retention. The O-linked attachment of β-N-acetylglucosamine to cardiac proteins is increased in cardiovascular disease and heart failure, and O-GlcNAc transferase (OGT) is the enzyme that catalyzes this addition. Deletion of OGT is embryonically lethal, and cardiomyocyte-specific OGT knockdown causes the exacerbation of heart failure. Stem cell therapy is currently a major focus of heart failure research, and it was recently discovered that OGT is intricately involved with stem cell differentiation. This article focuses on the relationship of OGT with epigenetics and pluripotency, and integrates OGT with several emerging areas of heart failure research, including calcium signaling.

KEYWORDS :

• CaMKII
• cardiac stem cells
• epigenetics
• heart failure
• OGT
• pluripotency

Financial & competing interests disclosure

This work was completed under funding from the NIH (HL-104549 to SA Marsh) and a William Townsend Porter Predoctoral Fellowship from the American Physiological Society (to HM Medford). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.