Development of a Quantitative Systems Pharmacology Model to Interrogate Mitochondrial Metabolism in Heart Failure.

ABSTRACT: The metabolic hallmarks of heart failure (HF) include diminished ATP hydrolysis potential and alterations in myocardial energy substrate metabolism, such as a switch in substrate utilization away from fatty acid (FA) to carbohydrate oxidation and reduced metabolic flexibility. However, the mechanisms underlying these phenomena and their potential contributions to impaired exercise tolerance are poorly understood. We developed a comprehensive quantitative systems pharmacology (QSP) model of mitochondrial metabolism to interrogate specific pathways hypothesized to contribute to reductions in reserve cardiac power output in heart failure. The aim of this work was to understand how changes in mitochondrial function and cardiac energetics associated with heart failure may affect exercise capaci

SUBMITTER: Meyer LF 

PROVIDER: S-EPMC12265515 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature