EPAS1 and Hypercholesterolemia: Different ceramide species dynamically interconvert and mediate adipose-liver interaction in vivo.92 Furthermore, cholesterol, a vital component in atherosclerosis, depends on oxygen for its synthesis.472 Paradoxically, hypoxia elevates cholesterol levels, heightening the risk of cardiovascular disease.473 Hepatic Cyp7a1 gene expression decreases due to elevated E4BP4, likely through HIF-2α activation and subsequent Rev-erbα inhibition, a circadian-related molecule (Fig. 5c).14 Hepatic HIF-2α activation (instead of HIF-1α) cause hypercholesterolemia.