In order to test this hypothesis, we injected WT and Ad-KO mice with adenoviral constructs overexpressing PCSK9 (AAV8-PCSK9), an enzyme that degrades hepatic low-density lipoprotein receptor (LDLr) and increases circulating proatherogenic lipoproteins comparable to hyperlipidemia observed in the well-established atherogenic Ldlr–/– mice (39, 40). The gene discussed is LDLR; the disease is hyperlipidemia.