Abstract
Several groups have demonstrated that PERM1 is a positive regulator of mitochondrial bioenergetics in the heart. However, conflicting results have emerged regarding whether PERM1 loss of function affects cardiac contractility. Here, we present data from a retrospective study compiling echocardiography data from all Perm1-knockout (Perm1-KO) mice and their wild-type (WT) littermates used for various molecular biology experiments in our laboratory between April 2022 and September 2023. This yielded an atypically large number of subjects per group—84 WT mice and 88 Perm1-KO mice. We analyzed echocardiography-derived parameters of left ventricular (LV) systolic function. The ejection fraction (EF) was 65.43 ± 7.13% in WT vs. 53.98 ± 8.80% in Perm1-KO mice (p = 5.21E-17, unpaired t-test). Other parameters showing statistically significant differences between WT and Perm1-KO (p < 0.05) included LV fractional shortening, LV diastolic and systolic diameters, LV anterior and posterior systolic wall thickness, LV posterior wall systolic thickening, stroke volume, and cardiac output. Importantly, this large cohort of echocardiography analyses revealed a broad range of cardiac contractile function among WT mice, and this degree of variability persisted in Perm1 KO; however, the entire distribution was shifted downward, suggesting that Perm1 deficiency reduces mean cardiac performance without altering intrinsic variability. Overall, our study indicates that constitutive Perm1 deletion leads to reduced contractility partially compensated by increased LV circumference. This study provides strong evidence that Perm1-KO causes specific remodeling of cardiac contractile function and provides a retrospective power analysis to guide future prospective studies.
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Data availability
The raw data (echocardiographic images) generated during the current study are available from the corresponding author on reasonable request. The quantification of all the raw data was performed using VevoLab software. All data exported from VevoLab software during this study are included in this published article and its Supplementary Information files.
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Acknowledgements
We thank Dr. Allison Tegge for her assistance with statistical analysis and valuable suggestions. We are also grateful to Dr. Robert Goudie for his generous support and for providing access to the echocardiography system in his laboratory. Additionally, we greatly appreciate the technical assistance provided by Jane L. Jourdan, Sydney Bui, and Katia Olmos.
Funding
This study was supported by NIH R01HL156667 (J.S.W.), NIH R01HL15667-02S (J.S.W.), FBRI Virginia Tech Carilion Operation Fund (J.S.W.), Seale Innovation Fund (J.S.W.), American Heart Association Postdoctoral Fellowship 24POST1186520 (K.S.), and Virginia Tech Research and Innovation Postdoctoral Scholarship (K.S.).
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A.Z. and K.S. collected the raw data. A.Z. and B.G. analyzed the data. A.Z. and J.S.W. wrote the main manuscript text. All authors reviewed the manuscript.
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J.S.W, A.V.Z, and K.S. are co-founders of a startup company Vectorial Corp. created for the purpose of translation of AAV-PERM1 vector therapy into clinical practice.
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Zaitsev, A.V., Sreedevi, K., Goode, B. et al. Analysis of systolic cardiac function in PERM1-knockout mice using large cohorts of animals. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37420-2
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DOI: https://doi.org/10.1038/s41598-026-37420-2
