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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
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
1Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China.
Insights
Circular RNA circGSE1 promotes blood vessel formation in aging endothelial cells by regulating the miR-323-5p/NRP1 pathway, offering a potential therapeutic target for age-related cardiovascular issues.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Aging Research
Background:
- Endothelial cells (ECs) are crucial in cardiovascular health, with aging impairing their function and contributing to disease.
- Circular RNAs (circRNAs) are implicated in cardiovascular diseases, but their role in age-related endothelial dysfunction and angiogenesis remains largely unknown.
Purpose of the Study:
- To identify a functional circRNA regulating angiogenesis in aging ECs.
- To elucidate the underlying molecular mechanism of this circRNA in promoting endothelial angiogenesis during aging.
Main Methods:
- CircRNA sequencing to identify differentially expressed circRNAs in old (OECs) versus young (YECs) endothelial cells.
- In vitro assays (proliferation, migration, tube formation) to assess circGSE1 function in OECs.
- In vivo mouse model (femoral artery ligation) to evaluate circGSE1's effect on angiogenesis in aging mice.
Main Results:
- circGSE1 was significantly downregulated in OECs compared to YECs.
- Overexpression of circGSE1 enhanced proliferation, migration, and tube formation in OECs in vitro.
- circGSE1 promoted blood flow recovery and angiogenesis in ischemic limbs of aging mice, acting via the miR-323-5p/NRP1 axis.
Conclusions:
- circGSE1 plays a vital role in promoting endothelial angiogenesis during aging.
- The circGSE1/miR-323-5p/NRP1 axis is a key mechanism regulating angiogenesis in aging ECs.
- This axis represents a promising therapeutic target for enhancing angiogenesis in aging-related cardiovascular conditions.
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.
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