Metabolic regulation of O-GlcNAc and cardiac function during hypertrophy
EMSL Project ID
50618
Abstract
Despite treatment advances, half of patients suffering from heart failure die within five years of diagnosis, while those who survive may live with severe disabilities. Cardiac hypertrophy poses a major risk factor for heart failure. Unraveling the mechanisms that mediate the inexorable evolution of hypertrophy to heart failure is essential to accelerate the development of new therapies for this common and devastating disease. Cardiac hypertrophy causes shifts in the metabolic profile towards increased reliance on glucose. This metabolic dysregulation is thought to contribute to the development of cardiac dysfunction; however the causal mechanisms linking these changes to cardiac function remain vague. Recent studies have found that posttranslational protein modifications by O-linked ?-N-acetylglucosamine (O-GlcNAc) increases globally during cardiac hypertrophy and heart failure. Generation of the O-GlcNAc moiety depends on shuttling glucose into an accessary pathway from glycolysis. Our central working hypothesis is that changes in substrate metabolism during hypertrophy affect functional compensation through O-GlcNAc signaling. We will test this hypothesis in a mouse model of cardiac hypertrophy from transverse aortic constriction.
Project Details
Start Date
2018-11-26
End Date
2021-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members