Rates of LDL entry and retention in mouse aorta are dissociated and predict the course of atherogenesis

To investigate capacity of LDL entry and retention changes during the pre-atherosclerotic phase, we measured gene expression at the inner curvature region of the aortic arch in the presence of normal and short-term high LDL plasma levels through RNA-seq Overall design: To set different LDL plasma levels but with the same hepatic LDL clearance rate, two groups of mice were treated with rAAV-PCSK9 and high-cholesterol diet (4% fat, 0.3% cholesterol), but in one of the groups the plasma LDL was kept at normal levels by treating with antisense oligonucleotides targeting Apob mRNA (Apob ASO) (normal aortas). The other group was treated with control antisense oligonucleotides (Ctrl ASO) (pre-atherosclerotic aortas). After 3.5 weeks with high or normal plasma LDL, gene expression changes were evaluated at the inner curvature region of the aortic arch.