More importantly, we identified that the serum levels of the cholesterol metabolite 27-hydroxycholesterol, which is the most abundant oxysterol in circulation and previously found to positively correlate with the development and progression of atherosclerosis both in humans and in rodents [37,38], was also upregulated in Apoe−/−/Hmgcr KI mice (Figure 2G–H and Fig. S2F), while serum bile acids remain comparable (Fig. S2G). Here, HMGCR is linked to atherosclerosis.