Abstract
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.