The combination of a high-fat diet and L-NAME successfully induced HFpEF in male FVB/N mice and significantly impaired myocardial ubiquitin-proteasome system performance.
Does a double-hit protocol of high-fat diet and L-NAME induce HFpEF and impair myocardial ubiquitin-proteasome system performance in FVB/N mice?
The double-hit protocol successfully induces an HFpEF phenotype in FVB/N mice and demonstrates that myocardial ubiquitin-proteasome system functioning is impaired during HFpEF.
p-value: p=0.0497
Heart failure with preserved ejection fraction (HFpEF) is a leading cause of death and disability, with its prevalence surpassing that of heart failure with reduced ejection fraction. Obesity and hypertension are often associated with HFpEF. HFpEF can be modeled through simultaneous metabolic and hypertensive stresses in male C57BL/6N mice provoked by a combination treatment of a high-fat diet (HFD) and constitutive nitric oxide synthase inhibition by Nω-nitro-L-arginine methyl-ester (L-NAME). Ubiquitin-proteasome system (UPS) dysfunction was detected in many forms of cardiomyopathy, but whether it occurs in HFpEF remains unknown. We report successful modeling of HFpEF in male FVB/N mice and, by taking advantage of a transgenic UPS reporter mouse, we have detected myocardial UPS functioning impairment during HFpEF, suggesting a pathogenic role for impaired protein degradation in the development and progression of HFpEF.
Lira et al. (Thu,) conducted a other in Heart failure with preserved ejection fraction (HFpEF) (n=13). High-fat diet (HFD) and L-NAME vs. Standard murine chow diet and water was evaluated on Myocardial ubiquitin-proteasome system (UPS) performance measured by GFPdgn protein levels (p=0.0497). The combination of a high-fat diet and L-NAME successfully induced HFpEF in male FVB/N mice and significantly impaired myocardial ubiquitin-proteasome system performance.
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