Intramyocardial injection of synthetic microRNAs (miRs) has recently been reported to be beneficial after myocardial infarction (MI). We conducted a randomized blinded study to evaluate the efficacy and reproducibility of this strategy in a mouse model of reperfused MI using rigorous methodology. Mice undergoing a 60-min coronary occlusion followed by reperfusion were randomly assigned to control miR, hsa-miR-199a-3p, hsa-miR-149-3p, or hsa-miR-149-5p mimic treatment. Intramyocardial injections of miRs were performed in the border zone right after reperfusion. At 8 weeks after MI, there were no significant differences in ejection fraction (EF) among groups (EF = 27.1 ± 0.4% in control group [n = 6] and 25.9 ± 0.5%, 26.0 ± 0.8%, and 26.6 ± 0.6% in hsa-miR-199a-3p, hsa-miR-149-3p, or hsa-miR-149-5p groups, respectively [n = 9 each]). Net change (delta) in EF at 8 weeks compared with day 3 after MI was - 4.1% in control and - 3.2%, - 2.4%, and - 0.4% in the miR-treated groups (P = NS). Assessment of cardiac function by hemodynamic studies (a method independent of echocardiography) confirmed that there was no difference in left ventricular systolic or diastolic function among groups. Consistent with the functional data, histological analysis showed no difference in scar size, cardiomyocyte area, capillary density, collagen content, or apoptosis among groups. In conclusion, this randomized, blinded study demonstrates that intramyocardial injection of a single dose of synthetic hsa-miR-199a-3p, hsa-miR-149-3p, or hsa-miR-149-5p mimic does not improve cardiac function or remodeling in a murine model of reperfused MI. The strategy of using synthetic miR mimics for cardiac repair after MI needs to be evaluated with rigorous preclinical studies before its potential clinical translation.

中文翻译：

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单剂量合成 microRNA-199a 或 microRNA-149 模拟物不会改善心肌梗塞小鼠模型中的心脏功能。

最近有报道称，在心肌梗塞 (MI) 后，心肌内注射合成的 microRNA (miRs) 是有益的。我们进行了一项随机盲法研究，以使用严格的方法评估该策略在再灌注 MI 小鼠模型中的有效性和可重复性。将接受 60 分钟冠状动脉闭塞然后再灌注的小鼠随机分配到对照 miR、hsa-miR-199a-3p、hsa-miR-149-3p 或 hsa-miR-149-5p 模拟治疗组。再灌注后立即在边界区进行 miRs 的心肌内注射。在 MI 后 8 周，各组之间的射血分数 (EF) 没有显着差异（对照组 [n = 6] EF = 27.1 ± 0.4% 和 25.9 ± 0.5%、26.0 ± 0.8% 和 26.6 ± 0.6%在 hsa-miR-199a-3p、hsa-miR-149-3p 或 hsa-miR-149-5p 组中，分别 [n = 9 个]）。与 MI 后第 3 天相比，8 周时 EF 的净变化 (delta) 在对照组中为 - 4.1%，在 miR 治疗组中为 - 3.2%、 - 2.4% 和 - 0.4% (P = NS)。通过血流动力学研究（一种独立于超声心动图的方法）对心脏功能的评估证实，各组之间的左心室收缩或舒张功能没有差异。与功能数据一致，组织学分析显示各组间瘢痕大小、心肌细胞面积、毛细血管密度、胶原蛋白含量或细胞凋亡无差异。总之，这项随机、盲法研究表明，心肌内注射单剂量的合成 hsa-miR-199a-3p、hsa-miR-149-3p 或 hsa-miR-149-5p 模拟物不会改善心脏功能或重塑在再灌注心肌梗死的小鼠模型中。