Inhibition of MicroRNA-92a Protects Against Ischemia/Reperfusion Injury in a Large-Animal Model
Inhibition of MicroRNA-92a Protects Against Ischemia/Reperfusion Injury in a Large-Animal Model
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DOI：
10.1161/circulationaha.113.001904
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发表时间：
2013-09-03
期刊：
影响因子：
37.8
通讯作者：
Dimmeler, Stefanie
中科院分区：
文献类型：
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作者：
Hinkel, Rabea;Penzkofer, Daniela;Dimmeler, Stefanie
背景MicroRNA (miR) 是转录后控制基因表达的小非编码 RNA。小动物研究表明，miR 可能为心血管疾病提供新的治疗靶点，例如通过 miR-92a 抑制剂对心肌梗死后的小鼠心脏进行心脏保护。由于 miR-92a 抑制剂在较大的临床前模型中的功能益处尚不清楚，因此我们评估了 miR-92a 抑制在猪缺血和再灌注模型中的治疗效果。 方法和结果 猪（每组 n=5）接受经皮缺血/再灌注（分别为 60 分钟/72 小时或 7 天）。通过导管局部（顺行或逆行）或全身（静脉注射）应用锁核酸修饰的反义 miR-92a (LNA-92a)。 LNA-92a 显着 (P
BackgroundMicroRNAs (miRs) are small noncoding RNAs that posttranscriptionally control gene expression. Small-animal studies suggest that miRs might offer novel therapeutic targets in cardiovascular diseases such as cardioprotection of murine hearts after myocardial infarction via miR-92a inhibitors. Because the functional benefits of miR-92a inhibitors in larger preclinical models are not known, we assessed the therapeutic efficacy of miR-92a inhibition in a porcine model of ischemia and reperfusion.Methods and ResultsPigs (n=5 per group) underwent percutaneous ischemia/reperfusion (60 min/72 h or 7 days, respectively). Locked nucleic acid-modified antisense miR-92a (LNA-92a) was applied either regionally (antegrade or retrograde) with a catheter or systemically (intravenously). LNA-92a significantly (P