HDL biology
Knocking down hepatic SR-BI raises CETP-mediated cholesteryl ester transfer from HDL to apoB lipoproteins and halves atherosclerotic lesion area in rabbits (Atherosclerosis 2012)
Original title: Inhibition of hepatic scavenger receptor-class B type I by RNA interference decreases atherosclerosis in rabbits
Using organ-selective RNA interference to silence hepatic scavenger receptor class B type I (SR-BI) in cholesterol-fed rabbits, a CETP-expressing species with a human-like lipoprotein profile, researchers reduced hepatic SR-BI mRNA by 80% after 2 weeks. SR-BI-silenced rabbits showed higher cholesteryl ester transfer from HDL to apoB-containing lipoproteins, lower HDL cholesterol, and higher VLDL cholesterol than controls. In a long-term study, this same lipoprotein-profile shift persisted alongside lower total cholesterol and, notably, a 50% reduction in relative atherosclerotic lesion area, suggesting SR-BI's role in atherogenesis in this CETP-expressing, human-like model may differ from its role in rodents.
Original abstract
Objective: Scavenger receptor-class B type I (SR-BI), the receptor for HDL-cholesterol, plays a key role in HDL metabolism, whole body cholesterol homeostasis, and reverse cholesterol transport. We investigated the in vivo impact of hepatic SR-BI inhibition on lipoprotein metabolism and the development of atherosclerosis employing RNA interference.
Methods: Small hairpin RNA plasmid specific for rabbit SR-BI was complexed with galactosylated poly-l-lysine, allowing an organ-selective, receptor-mediated gene transfer. Rabbits were fed a cholesterol-rich diet, and were injected with plasmid-complexes once a week.
Results: After 2 weeks of treatment hepatic SR-BI mRNA levels were reduced by 80% accompanied by reduced SR-BI protein levels and a modulation of the lipoprotein profile. Rabbits treated with SR-BI-specific plasmid-complexes displayed higher cholesteryl ester transfer from HDL to apoB-containing lipoproteins, lower HDL-cholesterol, and higher VLDL-cholesterol levels, when compared to controls. In a long-term study, this gene therapeutic intervention led to a similar modulation of the lipoprotein profile, to lower total cholesterol levels, and most importantly to a 50% reduction of the relative atherosclerotic lesion area.
Conclusion: Our results are another indication that the role of SR-BI in lipoprotein metabolism and atherogenesis in rabbits--a CETP-expressing animal model displaying a manlike lipoprotein profile may be different from the one found in rodents.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.