Transient Elevation in Cellular Glucose Uptake Exacerbates Pressure-Overload Induced Cardiac Hypertrophy and Dysfunction

To understand the long-term effects of these changes, we also performed sham or transverse aortic constriction (TAC) surgery at this four-week timepoint to induce pressure overload-mediated secondary stress. Mice were then followed for an additional 8 weeks and assessed for contractile function by echocardiography, cellular remodeling, and molecular analysis. Pressure overload led to an exacerbated hypertrophic response and cardiac dysfunction.

Subsequent qPCR-mediated expression analysis identified molecular changes akin to heart failure, worsened cardiac fibrosis, and impaired oxidative stress. CONCLUSIONS: These results indicate an altered transcriptome and DNA methylome upon prior transient enhanced glucose delivery, which evokes a glycemic memory response, responsible for long-term heart failure predisposition. We also identified molecular signatures of differential expression and methylation, as well as potential hubs that may provide novel targets for mechanistic understanding and therapeutic interventions.