Inhibition of hepatic scavenger receptor-class B type I by RNA interference decreases atherosclerosis in rabbits.
Atherosclerosis
; 222(2): 360-6, 2012 Jun.
Article
en En
| MEDLINE
| ID: mdl-22494625
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Antígenos CD36
/
ARN Interferente Pequeño
/
Interferencia de ARN
/
Aterosclerosis
/
Hígado
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Atherosclerosis
Año:
2012
Tipo del documento:
Article
País de afiliación:
Austria