Considering that there is a positive correlation between circ‐PIAS1‐5 expression in the plasma and aorta of ApoE−/− mice fed a high‐methionine diet, we further elucidated whether circ‐PIAS1‐5 can be used as a novel diagnostic biomarker for HHcy‐associated atherosclerosis. This evidence concerns the gene APOE and atherosclerosis.