Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Exp Cell Res. 2019 May 1;378(1):87-97. doi: 10.1016/j.yexcr.2019.03.012. Epub 2019 Mar 7.
MicroRNAs (miRNAs) have become potential targets for the treatment of heart failure (HF). It has been shown that miR-1 can reverse cardiac hypertrophy during the compensatory phase of HF development, but it is unknown whether miR-1 can still reverse cardiac dysfunction and improve cardiac remodeling after HF progresses to the decompensation stage. We established a mouse model of isoproterenol-induced HF and then injected miR-1a-3p agomir (agomir-1) into the tail vein. Echocardiography showed that the mice treated with agomir-1 had significantly increased ejection fraction and fractional shortening. These mice also showed a decrease in the N-terminal pro-B type natriuretic peptide (NT-proBNP) levels, but this remained higher than in controls. Cardiac hypertrophy, myocardial fibrosis, apoptosis, and glycogen deposition were reduced in mice treated with agomir-1. Furthermore, we found that supplementation of agomir-1 increased the expression of two mitochondrial DNA-encoded proteins, mitochondrially encoded NADH dehydrogenase 1 (ND1) and mitochondrially encoded cytochrome c oxidase I (COX1). In conclusion, our study found that miR-1a-3p alleviated the symptoms of ISO-induced HF in mice by enhancing mitochondrial ND1 and COX1. The results of this work may provide new therapeutic strategies for the treatment of HF patients.
微小 RNA（miRNAs）已成为心力衰竭（HF）治疗的潜在靶点。研究表明，miR-1 可在 HF 发展的代偿期逆转心肌肥厚，但尚不清楚 miR-1 是否仍可在 HF 进展至失代偿期后逆转心功能障碍并改善心脏重构。我们建立了异丙肾上腺素诱导的 HF 小鼠模型，然后将 miR-1a-3p 激动剂（agomir-1）注入尾静脉。超声心动图显示，agomir-1 处理的小鼠射血分数和短轴缩短率明显增加。这些小鼠的 N 末端 pro-B 型利钠肽（NT-proBNP）水平也降低，但仍高于对照组。agomir-1 处理的小鼠心肌肥厚、心肌纤维化、细胞凋亡和糖原沉积减少。此外，我们发现 agomir-1 的补充增加了两种线粒体 DNA 编码蛋白的表达，即线粒体编码烟酰胺腺嘌呤二核苷酸脱氢酶 1（ND1）和线粒体编码细胞色素 c 氧化酶 I（COX1）。总之，我们的研究发现 miR-1a-3p 通过增强线粒体 ND1 和 COX1 缓解了 ISO 诱导的 HF 小鼠的症状。这项工作的结果可能为 HF 患者的治疗提供新的治疗策略。
