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Related Concept Videos

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Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
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A Surgical Model of Heart Failure with Preserved Ejection Fraction in Tibetan Minipigs
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Lean ZSF1 rats in basic research on heart failure with preserved ejection fraction.

Petra Büttner1, Antje Augstein2, Mahmoud Abdellatif3,4

  • 1Department of Cardiology, Heart Center Leipzig at University of Leipzig, Leipzig, Germany.

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|December 12, 2024
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Summary

Lean ZSF1 rats with one mutant leptin receptor allele do not show altered heart failure with preserved ejection fraction (HFpEF) parameters. Genotype did not correlate with N-terminal pro-brain natriuretic peptide, cardiac inflammation, or left ventricular ejection fraction in these control animals.

Keywords:
HFpEF rat modelZSF1 genotypeZSF1 ratheart failure with preserved ejection fraction

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Area of Science:

  • Cardiovascular Research
  • Animal Models
  • Metabolic Syndrome

Background:

  • ZSF1 obese rats with two mutant leptin receptor alleles are a model for metabolic syndrome and heart failure with preserved ejection fraction (HFpEF).
  • Lean ZSF1 rats (L-ZSF1) typically serve as controls, but the impact of a single mutant leptin receptor allele on HFpEF parameters is not well understood.

Purpose of the Study:

  • To investigate whether a single mutant leptin receptor allele in L-ZSF1 rats influences HFpEF-related parameters.
  • To validate the genotype-phenotype relationship in L-ZSF1 rats as control subjects.

Main Methods:

  • Analysis of echocardiography and biochemical data from 165 L-ZSF1 rats (male and female) aged 6-32 weeks.
  • Genotyping and genotype-phenotype correlation analysis for HFpEF-relevant markers including N-terminal pro-brain natriuretic peptide (NT-proBNP), CD68 counts, left ventricular ejection fraction (LVEF), and E/e' ratio.

Main Results:

  • Genotype distribution in L-ZSF1 rats was consistent with Hardy-Weinberg equilibrium.
  • No significant association was found between genotype and CD68 counts, E/e' ratio, or NT-proBNP levels.
  • Left ventricular ejection fraction (LVEF) decreased with age from 25 weeks but was independent of genotype.

Conclusions:

  • Genotype validation in L-ZSF1 rats confirmed no association between the leptin receptor genotype and key HFpEF indicators.
  • These findings support the use of L-ZSF1 rats as appropriate controls in HFpEF research, as a single mutant allele does not confer HFpEF-related traits.