In 2012, it was shown that LDLR expressed in the surface of human macrophages were downregulated by PCSK9 produced by VSMC, reducing the ability of macrophages to internalize native LDL molecules and avoiding the formation of foam cells, indicating that PCSK9-stimulated macrophages reduce foam cells formation and hence, reduce atherosclerosis progression (35). This evidence concerns the gene PCSK9 and atherosclerosis.