Azuma Ryota, Shingu Yasushige, Gao Jingwen, Wakasa Satoru
Department of Cardiovascular Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kitaku, Sapporo 060-8638, Japan.
Int J Mol Sci. 2025 May 6;26(9):4422. doi: 10.3390/ijms26094422.
Percutaneous ventricular assist devices are utilized in cases of cardiogenic shock following acute myocardial infarction (AMI). However, the mechanism underlying the beneficial effects of LV unloading in AMI remains unclear. This study aimed to examine the impact of LV unloading on cardiac function, heart failure markers, and protein degradation (autophagy and ubiquitin-proteasome system: UPS) post AMI in rats. Nine-week-old male Lewis rats were randomized into non-AMI, AMI, non-AMI with LV unloading, and AMI with LV unloading groups. LV unloading was achieved through heterotopic heart-lung transplantation. Rats were euthanized 2 and 14 days after the procedure. Cardiac functional assessment was performed using Langendorff heart perfusion. RT-PCR and Western blot analyses were conducted using the LV myocardium. The rate pressure product was comparable between the non-AMI with LV unloading group and the AMI with LV unloading at 14 days. The atrial natriuretic factor tended to be suppressed by LV unloading. LV unloading had reducing effects on the expressions of p62, selectively degraded during autophagy, both 2 and 14 days after AMI. There was no effect on the parameters for the UPS. LV unloading has a mitigating effect on the deterioration of cardiac function following AMI. Autophagy, which was suppressed by AMI, was ameliorated by LV unloading.
经皮心室辅助装置用于急性心肌梗死(AMI)后心源性休克的病例。然而,左心室卸载在AMI中产生有益作用的潜在机制仍不清楚。本研究旨在探讨左心室卸载对大鼠AMI后心脏功能、心力衰竭标志物及蛋白质降解(自噬和泛素-蛋白酶体系统:UPS)的影响。将9周龄雄性Lewis大鼠随机分为非AMI组、AMI组、左心室卸载的非AMI组和左心室卸载的AMI组。通过异位心肺移植实现左心室卸载。术后2天和14天对大鼠实施安乐死。使用Langendorff心脏灌注法进行心脏功能评估。使用左心室心肌进行RT-PCR和蛋白质印迹分析。在14天时,左心室卸载的非AMI组和左心室卸载的AMI组之间的心率血压乘积相当。左心室卸载倾向于抑制心房利钠因子。左心室卸载对AMI后2天和14天自噬过程中选择性降解的p62表达有降低作用。对UPS的参数没有影响。左心室卸载对AMI后心脏功能的恶化有缓解作用。AMI所抑制的自噬通过左心室卸载得到改善。