Overexpression of long non-coding RNA ANRIL promotes post-ischaemic angiogenesis and improves cardiac functions by targeting Akt.

Abstract

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.

• Authors: Qun Huang, Miao Pan, Ji-Peng Zhou, Fei Yin
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 12 Pg. 6860-6868 (06 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32400082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• CDKN2B antisense RNA, human
• RNA, Long Noncoding
• Insulin-Like Growth Factor I
• Nitric Oxide Synthase Type III
• Proto-Oncogene Proteins c-akt
• Glucose
• Oxygen

Topics

• Adenoviridae (metabolism)
• Animals
• Cell Movement (genetics)
• Glucose (deficiency)
• Heart (physiopathology)
• Human Umbilical Vein Endothelial Cells (metabolism, pathology)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Male
• Mice, Inbred C57BL
• Myocardial Ischemia (genetics, pathology, physiopathology)
• Neovascularization, Physiologic (genetics)
• Nitric Oxide Synthase Type III (metabolism)
• Oxygen
• Phosphorylation
• Protein Binding
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• Recovery of Function
• Signal Transduction
• Up-Regulation (genetics)