Angiogenesis is critical for re‐establishing the blood supply to the surviving myocardium after myocardial infarction (MI). Long non‐coding RNA ANRIL (lncRNA‐ANRIL) has been reported to regulate endothelial functions in cardiovascular diseases. This study was to determine the role of lncRNA‐ANRIL in Akt regulation and cardiac functions after MI. Human umbilical vein endothelial cells (HUVECs) were exposed to oxygen‐glucose deprivation (OGD) to mimic in vivo ischaemia. The MI model in mice was induced by ligating left anterior descending coronary artery. OGD remarkably decreased lncRNA‐ANRIL expression level, reduced the phosphorylated levels of Akt and eNOS proteins, and inhibited NO release and cell viability, which were duplicated by shRNA‐mediated gene knockdown of lncRNA‐ANRIL. Conversely, all these effects induced by OGD were abolished by adenovirus‐mediated overexpression of lncRNA‐ANRIL in HUVECs. Further, OGD impaired cell migrations and tube formations in HUVECs, which were reversed by lncRNA‐ANRIL overexpression or Akt up‐regulation. RNA immunoprecipitation analysis indicated that the affinity of lncRNA‐ANRIL to Akt protein was increased in OGD‐treated cells. In animal studies, adenovirus‐mediated lncRNA‐ANRIL overexpression increased the phosphorylated levels of Akt and eNOS, promoted post‐ischaemic angiogenesis and improved heart functions in mice with MI surgery. LncRNA‐ANRIL regulates Akt phosphorylation to improve endothelial functions, which promotes angiogenesis and improves cardiac functions in mice following MI. In this perspective, targeting lncRNA‐ANRIL/Akt may be considered to develop a drug to treat angiogenesis‐related diseases.

中文翻译：

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长的非编码RNA ANRIL的过表达通过靶向Akt促进缺血后血管生成并改善心脏功能。

血管生成对于在心肌梗塞（MI）后重新建立存活的心肌的血液供应至关重要。据报道，长的非编码RNA ANRIL（lncRNA-ANRIL）可以调节心血管疾病的内皮功能。本研究旨在确定lncRNA-ANRIL在MI后Akt调节和心脏功能中的作用。将人脐静脉内皮细胞（HUVEC）暴露于氧葡萄糖剥夺（OGD）以模拟体内局部缺血。结扎左冠状动脉前降支可诱发小鼠MI模型。OGD显着降低了lncRNA-ANRIL的表达水平，降低了Akt和eNOS蛋白的磷酸化水平，并抑制了NO的释放和细胞活力，这可通过shRNA介导的lncRNA-ANRIL的基因敲除来复制。反过来，OGD诱导的所有这些作用均被腺病毒介导的HUVEC中lncRNA-ANRIL的过表达所消除。此外，OGD损害了HUVEC中的细胞迁移和管形成，而lncRNA-ANRIL过表达或Akt上调逆转了OGD。RNA免疫沉淀分析表明，在OGD处理的细胞中，lncRNA‐ANRIL对Akt蛋白的亲和力增加。在动物研究中，腺病毒介导的lncRNA-ANRIL过表达增加了MI手术小鼠的Akt和eNOS磷酸化水平，促进了缺血后血管生成并改善了心脏功能。LncRNA-ANRIL调节Akt磷酸化以改善内皮功能，从而促进血管生成并改善MI后小鼠的心脏功能。从这个角度来看，