Table 3.

circRNAs associated with atherosclerosis

CircRNA/miRNA interaction
CircRNA	miRNA	Protein target	Findings of the study	Methods	Reference
CircRNA‑0044073	miR‑107	JAK/STAT	CircRNA‑0044073 is upregulated in atherosclerosis and promotes the proliferation and invasion of cells by targeting miR‑107 and activating the JAK/STAT signalling pathway	RT-qPCR in blood cells from patients with atherosclerosis and healthy controls (n = 20 total). RNA pulldown for miRNA interaction.	Shen et al 2019 [110]
Circ_CHFR	miR-370	FOXO1	Knock down of circ_CHFR inhibits the proliferation and migration of VSMCs in vitro	Microarray on human vascular smooth muscle cells (VSMCs). Luciferase reporter assay for miRNA interaction	Yang et al 2019 [106]
Circ_CHFR	miR-214-3p	Wnt3/β-catenin pathway	Circ_CHFR was up-regulated in atherosclerotic serum and ox-LDL-stimulated VSMC. Circ_CHFR regulated cell growth, migration, and inflammation via regulating the expression of Wnt3 as a competitive endogenous RNA (ceRNA) of miR-214 in ox-LDL-treated VSMCs	RT-qPCR in atherosclerotic (n = 32) and control patient’s serum (n = 32). Cell model of atherosclerosis in (VSMCs) with oxidized low-density lipoprotein. Luciferase reporter assay for miRNA interaction	Zhuang et al 2020 [107]
Circ-SATB2	miR-939	Stromal Interaction Molecule 1 (STIM1)	Circ-SATB2 and STIM1 up-regulated in proliferative VSMCs, miR-939 down-regulated. Circ-SATB2 can regulate VSMC phenotypic differentiation, proliferation, apoptosis and migration by promoting the expression of STIM1	RT-qPCR in VSMCs. Dual luciferase assay for miRNA interaction	Mao et al 2018 [112]
Circ-Sirt1	miR-132/212	Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)	Circ-Sirt1 inhibits inflammatory phenotypic switching of VSMCs. Circ-Sirt1 controls NF-κB activation via enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells	RT-qPCR and microarray in human arterial tissues (11 atherosclerotic, 14 control), human plasma (20 CAD, 20 control) and rat VSMCs. RNA pulldown for miRNA interaction	Kong et al 2019 [111]
Circ_0003204	miR-370-3p	TGFβR2/phosph-SMAD3	Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis	RT-qPCR in human aorta endothelial cells (HAECs). Luciferase activity assay	Zhang et al 2019 [108]
Circ_RUSC2	miR-661	Tyrosine-protein kinase (SYK)	Circ_RUSC2 can promote the expression of SYK, a target gene of miR-661, and regulates VSMC proliferation, apoptosis, phenotypic modulation, and migration	RT-qPCR in human coronary artery smooth muscle cells. Dual luciferase assay	Sun et al 2019 [113]
CircRNA/Protein interaction
CircRNA	Protein target		Findings of the study	Methods	Reference
CircANRIL	Pescadillo Homologue 1 (PES1)		Binds pescadillo homologue 1 (PES1) to prevent rRNA maturation. This induces nucleolar stress and p53 activation which leads to apoptosis and proliferation inhibition. Atheroprotection is achieved by culling over-proliferating cell types in atherosclerotic plaques.	RT-qPCR for circRNA expression from peripheral blood mononuclear cell (PBMC), human primary tissues and cells. CAD patients (n = 2,280) undergoing coronary angiography. Also, human endarterectomy specimens (n = 218) collected from patients undergoing vascular surgery. GWAS for cells overexpressing circANRIL. λN-peptide-mediated pull-down of circANRIL-bound proteins	Holdt et al 2016 [65]
Mechanism unknown
CircRNA	Findings of the study			Methods	Reference
CircANRIL	Reduced circANRIL expression could prevent coronary AS by reducing vascular EC apoptosis and inflammatory factor expression			Atherosclerosis rat model (n = 60) 5 groups: control, model, empty vector group, over-expressed circANRIL group and low-expressed circANRIL group. serum lipids, apoptosis, protein and mRNA levels analysed in the 5 groups	Song et al 2017 [102]
Hsa_circ_0003204	Hsa_circ_0003204 was notably upregulated in HUVECs treated with oxidized low-density lipoprotein indicating may be involved in the pathogenesis of atherosclerosis. Knockdown boosted the proliferation, migration, and invasion of oxLDL-induced HUVECs, suggesting that hsa_circ_0003204 may slow down the repair of vascular endothelial cell injury.			RT-PCR from (OxLDL) human umbilical vein endothelial cells (HUVECs)	Liu et al 2020 [109]