Analysis of Systolic Cardiac Function in PERM1-knockout Mice: Insights from A Retrospective Study in Large Cohorts of...

Several groups demonstrated that PERM1 is a positive regulator of mitochondrial bioenergetics in the heart. However, discrepant results have emerged with regard to whether PERM1 loss-of-function affect cardiac contractility. Here we present data from a retrospective study collecting echocardiography data from all Perm1 knockout (Perm1-KO) mice and their wildtype (WT) littermates used for various molecular biological experiments in our lab between April of 2022 and September of 2023. This yielded an atypically large number of subjects per group, 84 WT mice and 88 Perm1-KO mice. We analyzed Echo-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 yielding p < 0.00000000000000004 using unpaired t-test. Other parameters which reached statistically significant difference between WT and Perm1-KO (at 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. Changes caused by constitutive Perm1-KO can be conceptualized as reduced contractility partially compensated by increased LV circumference. This study provides a strong evidence that Perm1-KO causes a specific remodeling of cardiac contractility and provides retrospective power analysis which can be useful for future prospective studies.