PCSK9 and hyperlipidemia: ApoE−/− mice are, like LDLr−/− mice, a severe model for hyperlipidemia, and due to the absence of a functional apoE-LDLr-mediated clearance pathway, these mice do not respond well to lipid-lowering drugs (e.g., statins [10], PCSK9 inhibitors [11]) and therefore cannot be used for the evaluation of combination treatment.