APOE and familial hypercholesterolemia: Other studies using apolipoprotein E knockout (ApoE–/–), an important protein in fat metabolism, or low-density lipoprotein receptor knockout (Ldlr–/–) models of hypercholesterolemia have shown that these mice also have severe lymphatic dysfunction, suggesting the interaction between elevated cholesterol levels and lymphatic function may be bidirectional (Lim et al., 2009; Milasan et al., 2019).