Research Paper Volume 14, Issue 7 pp 3049—3069

Circular RNA circGSE1 promotes angiogenesis in ageing mice by targeting the miR-323-5p/NRP1 axis

Jiacong Qiu1,2,3, , Rencong Chen1,2,3, , Lei Zhao1,2,3, , Chong Lian4, , Zhen Liu1,2,3, , Xiaonan Zhu5, , Jin Cui1,2,3, , Siwen Wang1,2,3, , Mingshan Wang1,2,3, , Yingxiong Huang6, , Shenming Wang1,2,3, , Jinsong Wang1,2,3, ,

  • 1 Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China
  • 2 National-Local Joint Engineering Laboratory of Vascular Disease Treatment, Guangzhou 510080, Guangdong, China
  • 3 Guangdong Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou 510080, Guangdong, China
  • 4 Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, China
  • 5 Department of Pharmacology Laboratory, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China
  • 6 Department of Emergency, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China

Received: September 21, 2021       Accepted: February 15, 2022       Published: April 1, 2022
How to Cite

Copyright: © 2022 Qiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Age is an important factor in many cardiovascular diseases, in which endothelial cells (ECs) play an important role. Circular RNAs (circRNAs) have been reported in many cardiovascular diseases, but their role in ageing EC-related angiogenesis is unclear. We aimed to identify a functional circRNA that regulates angiogenesis during ageing and explore its specific mechanism. In this study, we searched for differentially expressed circRNAs in old endothelial cells (OECs) and young endothelial cells (YECs) by circRNA sequencing and found that circGSE1 was significantly downregulated in OECs. Our study showed that circGSE1 could promote the proliferation, migration and tube formation of OECs in vitro. In a mouse model of femoral artery ligation and ischemia, circGSE1 promoted blood flow recovery and angiogenesis in the ischemic limbs of ageing mice. Mechanistically, we found that overexpressing circGSE1 reduced miR-323-5p expression, increased neuropilin-1 (NRP1) expression, and promoted proliferation, migration, and tube formation in OECs, while knocking down circGSE1 increased miR-323-5p expression, reduced NRP1 expression, and inhibited proliferation, migration, and tube formation in YECs. During EC ageing, circGSE1 may act through the miR-323-5p/NRP1 axis and promote endothelial angiogenesis in mice. Finally, the circGSE1/miR-323-5p/NRP1 axis could serve as a potential and promising therapeutic target for angiogenesis during ageing.


circGSE1: circular RNA GSE1; NRP1: neuropilin-1; GSE1: genetic suppressor element 1; OECs: old endothelial cells; YECs: young endothelial cells; MAECs: mouse aortic endothelial cells; miRNA: microRNA; FISH: Fluorescence in situ hybridization; RIP: RNA Immunoprecipitation; qRT-PCR: quantitative real-time PCR.