The double-hit protocol induces HFpEF and impairs myocardial ubiquitin-proteasome system performance in FVB/N mice

Frontiers in Physiology

Physiology

Jack O. Sternburg¹  Samiksha Giri¹  Jose R. Lira¹  Andrew L. Guymon¹  Liuqing Yang¹  Xuejun Wang² 

[1] Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Vermillion, SD, United States;null;

关键词: heart failure with preserved ejection fraction (HFpEF);    high fat diet (HFD);    Nω-nitro-L-arginine methyl-ester (L-NAME);    ubiquitin-proteasome system (UPS);    FVB/N mice;   

DOI  :  10.3389/fphys.2023.1208153

 received in 2023-04-18, accepted in 2023-05-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Lira, Guymon, Yang, Sternburg, Giri and Wang.