射血分数保留的心力衰竭
心力衰竭
医学
内科学
蛋白酶体
泛素
一氧化氮
心脏病学
射血分数
心肌病
内分泌学
化学
生物化学
基因
作者
José Antonio López de Lira,Andrew L. Guymon,Liuqing Yang,Jack O. Sternburg,Samiksha Giri,Xuejun Wang
标识
DOI:10.3389/fphys.2023.1208153
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.
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