Lean ZSF1 rats in basic research on heart failure with preserved ejection fraction

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.