Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Department of Cardiology, Heilongjiang Provincial People's Hospital, Harbin 150086, China.
Biomed Res Int. 2021 Feb 18;2021:3287053. doi: 10.1155/2021/3287053. eCollection 2021.
Oxidative stress is a crucial factor and key promoter of a variety of cardiovascular diseases associated with cardiomyocyte injury. Emerging literatures suggest that pyroptosis plays a key role in cardiac damages. However, whether pyroptosis contributes to cardiomyocyte injury under oxidative stress and the underlying molecular mechanisms are totally unclear. This study was designed to investigate the potential role of pyroptosis in HO-induced cardiomyocyte injury and to elucidate the potential mechanisms. Primary cardiomyocytes from neonatal Wistar rats were utilized. These myocytes were treated with different concentrations of HO (25, 50, and 100 M) for 24 h to induce oxidative injury. Our results indicated that mRNA and protein levels of ASC were remarkably upregulated and caspase-1 was activated. Moreover, the expressions of inflammatory factors IL-1 and IL-18 were also increased. Luciferase assay showed that miR-599 inhibited ASC expression through complementary binding with its 3'UTR. MiR-599 expression was substantially reduced in HO-treated cardiomyocytes. Upregulation of miR-599 inhibited cardiomyocyte pyroptosis under oxidative stress, and opposite results were found by decreasing the expression of miR-599. Consistently, miR-599 overexpression ameliorated cardiomyocyte injury caused by HO. Therefore, miR-599 could be a promising therapeutic approach for the management of cardiac injury under oxidative condition.
氧化应激是与心肌细胞损伤相关的多种心血管疾病的关键因素和主要促进剂。新出现的文献表明，细胞焦亡在心脏损伤中起关键作用。然而，细胞焦亡是否在氧化应激下导致心肌细胞损伤以及潜在的分子机制尚不清楚。本研究旨在探讨细胞焦亡在 HO 诱导的心肌细胞损伤中的潜在作用，并阐明潜在的机制。使用新生 Wistar 大鼠的原代心肌细胞。这些心肌细胞用不同浓度的 HO（25、50 和 100μM）处理 24 小时以诱导氧化损伤。我们的结果表明，ASC 的 mRNA 和蛋白水平显著上调，caspase-1 被激活。此外，炎症因子 IL-1 和 IL-18 的表达也增加。荧光素酶测定表明，miR-599 通过与 3'UTR 互补结合抑制 ASC 的表达。HO 处理的心肌细胞中 miR-599 的表达显著降低。miR-599 的上调抑制了氧化应激下的心肌细胞焦亡，而降低 miR-599 的表达则产生相反的结果。一致地，miR-599 的过表达改善了 HO 引起的心肌细胞损伤。因此，miR-599 可能是氧化条件下心脏损伤管理的有前途的治疗方法。
