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PERM1基因敲除小鼠的收缩期心脏功能分析:来自大型动物队列回顾性研究的见解

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

作者信息

Zaitsev Alexey V, Sreedevi Karthi, Goode Brianna, Warren Junco S

机构信息

Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech.

出版信息

Res Sq. 2025 Aug 13:rs.3.rs-6204170. doi: 10.21203/rs.3.rs-6204170/v1.

Abstract

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 knockout (-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 -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 P-KO yielding p < 0.00000000000000004 using unpaired t-test. Other parameters which reached statistically significant difference between WT and -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 -KO can be conceptualized as reduced contractility partially compensated by increased LV circumference. This study provides a strong evidence that -KO causes a specific remodeling of cardiac contractility and provides retrospective power analysis which can be useful for future prospective studies.

摘要

多个研究小组表明,PERM1是心脏线粒体生物能量学的正向调节因子。然而,关于PERM1功能丧失是否会影响心脏收缩力,出现了不一致的结果。在此,我们展示了一项回顾性研究的数据,该研究收集了2022年4月至2023年9月期间我们实验室用于各种分子生物学实验的所有基因敲除(-KO)小鼠及其野生型(WT)同窝小鼠的超声心动图数据。这使得每组的研究对象数量异常多,84只WT小鼠和88只-KO小鼠。我们分析了左心室(LV)收缩功能的超声心动图衍生参数。使用非配对t检验,WT组的射血分数(EF)为65.43±7.13,而P-KO组为53.98±8.80,p<0.00000000000000004。WT和-KO之间达到统计学显著差异(p<0.05)的其他参数包括左心室缩短分数、左心室舒张和收缩直径、左心室前壁和后壁收缩期厚度、左心室后壁收缩期增厚、每搏输出量和心输出量。组成型-KO引起的变化可理解为收缩力降低,部分由左心室周长增加来代偿。这项研究提供了强有力的证据,证明-KO会导致心脏收缩力的特定重塑,并提供了回顾性功效分析,这对未来的前瞻性研究可能有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d427/12363925/82d09bf7170f/nihpp-rs6204170v1-f0001.jpg

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