Extending these key findings to the atherosclerotic lesion, as M1 macrophages can develop into M2 macrophages after Nr4a1 induction (43), and deletion of Nr4a1 results in M1 polarized macrophages and increased atherosclerosis (44), it is possible that the environment of the atherosclerotic lesion could affect the M1 macrophages resulting in a failure to upregulate Nr4a1 and prevents the differentiation into M2 cells (Figure 1). This evidence concerns the gene NR4A1 and atherosclerosis.