Recent mechanistic investigation, using multiple mouse models (apoE KO, LDLR KO, recombination activation gene (RAG) 2 KO, CD36 KO, CARD9 KO and combinations) to rule out effects of the adaptive immune system and gut microbiota, has shown that CARD9 deficiency increased atherosclerosis lesion burden, with marked enhancement in macrophage and necrotic core lesion areas (63). This evidence concerns the gene LDLR and atherosclerosis.