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<p>Atherosclerosis (AS) is a chronic vascular disorder driven by endothelial dysfunction and inflammation, yet the roles of circular RNAs (circRNAs) in this process remain incompletely defined. Here, we identified circ0005699 as a significantly upregulated circRNA (fold change &gt; 2, <i>P</i> &lt; 0.05) in ox-LDL-treated macrophages and endothelial cells and confirmed its circular structure and stability by divergent PCR, RNase R resistance, and actinomycin D assays. qRT‒PCR analysis revealed elevated circ0005699 expression in serum from AS patients compared with that in serum from matched controls (<i>n</i> = 10 pairs, <i>P</i> &lt; 0.01). Functional studies revealed that circ0005699 knockdown enhanced endothelial proliferation and tube formation, whereas overexpression suppressed angiogenesis. Mechanistically, circ0005699 acts as a sponge for miR-636, thereby upregulating solute carrier family 7 member 5 (SLC7A5) activity and activating mTORC1 signalling, which inhibits autophagy. In parallel, circ0005699 interacts with the RNA demethylase FTO through its N-terminus, stabilizing EGR1 mRNA by reducing m6A modification. Increased EGR1 expression promoted inflammatory responses (IL-6, IL-1β, and ICAM-1) while limiting endothelial proliferation, and these effects were abolished by EGR1 knockdown. Together, these findings define circ0005699 as a stable, upregulated circRNA that orchestrates AS progression through both the circ0005699/miR-636/SLC7A5-mTORC1/autophagy axis and the circ0005699/FTO-EGR1 inflammatory pathway, providing a potential biomarker and therapeutic target in AS.</p>

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Circ005699 regulates ox-LDL-induced vascular endothelial cell proliferation, autophagy and inflammation by sponging miR-636 and interacting with FTO.

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Wen’ai Chen,
  • Jialei Hu,
  • Han Chen,
  • Feiming Ye,
  • Kaiqi Lv

摘要

Atherosclerosis (AS) is a chronic vascular disorder driven by endothelial dysfunction and inflammation, yet the roles of circular RNAs (circRNAs) in this process remain incompletely defined. Here, we identified circ0005699 as a significantly upregulated circRNA (fold change > 2, P < 0.05) in ox-LDL-treated macrophages and endothelial cells and confirmed its circular structure and stability by divergent PCR, RNase R resistance, and actinomycin D assays. qRT‒PCR analysis revealed elevated circ0005699 expression in serum from AS patients compared with that in serum from matched controls (n = 10 pairs, P < 0.01). Functional studies revealed that circ0005699 knockdown enhanced endothelial proliferation and tube formation, whereas overexpression suppressed angiogenesis. Mechanistically, circ0005699 acts as a sponge for miR-636, thereby upregulating solute carrier family 7 member 5 (SLC7A5) activity and activating mTORC1 signalling, which inhibits autophagy. In parallel, circ0005699 interacts with the RNA demethylase FTO through its N-terminus, stabilizing EGR1 mRNA by reducing m6A modification. Increased EGR1 expression promoted inflammatory responses (IL-6, IL-1β, and ICAM-1) while limiting endothelial proliferation, and these effects were abolished by EGR1 knockdown. Together, these findings define circ0005699 as a stable, upregulated circRNA that orchestrates AS progression through both the circ0005699/miR-636/SLC7A5-mTORC1/autophagy axis and the circ0005699/FTO-EGR1 inflammatory pathway, providing a potential biomarker and therapeutic target in AS.