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 Qiu^1,^2,³, Rencong Chen^1,^2,³, Lei Zhao^1,^2,³, Chong Lian⁴, Zhen Liu^1,^2,³, Xiaonan Zhu⁵, Jin Cui^1,^2,³, Siwen Wang^1,^2,³, Mingshan Wang^1,^2,³, Yingxiong Huang⁶, Shenming Wang^1,^2,³, Jinsong Wang^1,^2,³

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

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

https://doi.org/10.18632/aging.203988

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.

Abstract

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.