Blunted Cardiac Mitophagy in Response to Metabolic Stress Contributes to HFpEF.

ABSTRACT:

Background

Metabolic remodeling and mitochondrial dysfunction are hallmarks of heart failure with reduced ejection fraction. However, their role in the pathogenesis of HF with preserved ejection fraction (HFpEF) is poorly understood.

Methods

In a mouse model of HFpEF, induced by high-fat diet and Nω-nitrol-arginine methyl ester, cardiac energetics was measured by ³¹P nuclear magnetic resonance (NMR) spectroscopy and substrate oxidation profile was assessed by ¹³C-isotopmer analysis. Mitochondrial functions were assessed in the heart tissue and human induced pluripotent stem cell-derived cardiomyocytes.

Results

HFpEF hearts presented a lower phosphocreatine content and a reduced phosphocreatine/ATP ratio, similar to that in heart failure with redu

SUBMITTER: Yoshii A 

PROVIDER: S-EPMC11502249 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature