Institute of Biochemistry & Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada.
Department of Anesthesiology, Columbia University Medical Center, 622 West 168th Street, New York, NY, 10032, USA.
Cell Stress Chaperones. 2021 May;26(3):541-548. doi: 10.1007/s12192-021-01199-0. Epub 2021 Mar 4.
Anesthetics such as isoflurane are known to cause apoptosis in the developing mammalian brain. However, isoflurane may have protective effects on the heart via relieving ischemia and downregulating genes related to apoptosis. Ischemic preconditioning, e.g. through the use of low levels of carbon monoxide (CO), has promise in preventing ischemia-reperfusion injury and cell death. However, it is still unclear how it either triggers the stress response in neonatal hearts. For this reason, thirty-three microRNAs (miRNAs) known to be differentially expressed following anesthesia and/or ischemic or hypoxic heart damage were investigated in the hearts from neonatal mice exposed to isoflurane or low level of CO, using an air-exposed control group. Only miR-93-5p increased with isoflurane exposure, which may be associated with the suppression of cell death, autophagy, and inflammation. By contrast, twelve miRNAs were differentially expressed in the heart following CO treatment. Many miRNAs previously shown to be responsible for suppressing cell death, autophagy, and myocardial hypertrophy were upregulated (e.g., 125b-3p, 19-3p, and 21a-5p). Finally, some miRNAs (miR-103-3p, miR-1a-3p, miR-199a-1-5p) which have been implicated in regulating energy balance and cardiac contraction were also differentially expressed. Overall, this study demonstrated that CO-mediated miRNA regulation may promote ischemic preconditioning and cardioprotection based on the putative protective roles of the differentially expressed miRNAs explored herein and the consistency of these results with those that have shown positive effects of CO on heart viability following anesthesia and ischemia-reperfusion stress.
麻醉剂，如异氟烷，已知会导致哺乳动物大脑发育中的细胞凋亡。然而，异氟烷可能通过缓解缺血和下调与细胞凋亡相关的基因对心脏具有保护作用。缺血预处理，例如通过使用低水平的一氧化碳（CO），在预防缺血再灌注损伤和细胞死亡方面具有很大的潜力。然而，它如何在新生心脏中引发应激反应仍不清楚。出于这个原因，研究人员在暴露于异氟烷或低水平 CO 的新生小鼠心脏中，调查了已知在麻醉和/或缺血或缺氧性心脏损伤后表达差异的 33 个 microRNAs（miRNAs），使用空气暴露的对照组。只有 miR-93-5p 在异氟烷暴露后增加，这可能与细胞死亡、自噬和炎症的抑制有关。相比之下，CO 处理后心脏中有 12 个 miRNAs 表达差异。许多先前被证明负责抑制细胞死亡、自噬和心肌肥大的 miRNAs 上调（例如，125b-3p、19-3p 和 21a-5p）。最后，一些 miRNAs（miR-103-3p、miR-1a-3p、miR-199a-1-5p）也参与调节能量平衡和心脏收缩，它们的表达也存在差异。总的来说，这项研究表明，基于探索的差异表达 miRNAs 的假定保护作用以及这些结果与 CO 对麻醉和缺血再灌注应激后心脏活力的积极影响的结果的一致性，CO 介导的 miRNA 调节可能促进缺血预处理和心脏保护。
