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October 9, 2025Circulation Research

Abstract Wed082: Integrated Systems Biology Identifies Disruptions In Mitochondrial Function And Metabolism As Key Contributors To HFpEF

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Key result

HFpEF model shows ~25% lower mitochondrial respiration alongside impaired calcium uptake.

  • p<0.05
  • p<0.01

Authors

AGAndrew GibbUniversity of LouisvilleKLKyle B. LaPennaPennsylvania State UniversityRGRyan B. GasparUniversity of Pennsylvania

Discussion

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Implication

Observational analysis uncovers metabolic shifts and mitochondrial dysfunction in HFpEF, indicating key pathways for intervention.

Key Points

  • Transcriptional analysis revealed significant changes in 5,691 genes in ZSF1-obese rats, linking mitochondrial dysfunction to HFpEF.
  • Metabolic profiling indicated a shift from β-oxidation to glycolysis in hypertensive rats, suggesting altered energy metabolism.
  • Integrated omics highlighted reduced respiratory rates by ~25% in ZSF1-obese rats, indicating compromised mitochondrial function.
  • Analysis of cardiomyocyte structure showed cristae disorganization and significant lipid droplet accumulation in HFpEF hearts.

PICO

P
Population
Male, 14-week-old ZSF1-obese rats, ZSF1-lean hypertensive controls, and WKY controls undergoing physiological and molecular phenotyping.
E
Exposure / Comparator
ZSF1-obese phenotype (hypertension + metabolic syndrome) vs ZSF1-lean hypertensive controls and WKY controls
O
Primary Outcome
Metabolic and transcriptional signatures, mitochondrial respiration, and Ca2+ handling

Cite This Study

Gibb et al. (2025) studied HFpEF. ZSF1-obese phenotype (hypertension + metabolic syndrome) vs. ZSF1-lean hypertensive controls and WKY controls was evaluated on Metabolic and transcriptional signatures, mitochondrial respiration, and Ca2+ handling. ZSF1-obese HFpEF rats demonstrated significant downregulation of mitochondrial energy pathways, an ~25% reduction in respiratory rates (p<0.05), and failed Ca2+ uptake (p<0.01) compared to controls.

synapsesocial.com/papers/68e77f09d1c187e1c108fb0dhttps://doi.org/10.1161/res.137.suppl_1.wed082
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Integrated Systems Biology Identifies Disruptions in Mitochondrial Function and Metabolism as Key Contributors to HFpEF2025 · 13 citations
  2. 2Integrated systems biology identifies disruptions in mitochondrial function and metabolism as key contributors to heart failure with preserved ejection fraction (HFpEF)2024 · 3 citations
  3. 3Acetylation and phosphorylation changes to cardiac proteins in experimental HFpEF due to metabolic risk reveal targets for treatment2022 · 30 citations
  4. 4Multi-omic profiling of human left ventricle uncovers energy deprivation and extracellular matrix remodeling in obese HFpEF2026 · 1 citations
  5. 5Molecular Signature of HFpEF2021 · 26 citations