Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Demetz, E; Tancevski, I; Duwensee, K; Stanzl, U; Huber, E; Heim, C; Handle, F; Theurl, M; Schroll, A; Tailleux, A; Dietrich, H; Patsch, JR; Eller, P; Ritsch, A.
Inhibition of hepatic scavenger receptor-class B type I by RNA interference decreases atherosclerosis in rabbits.
Atherosclerosis. 2012; 222(2):360-366
Doi: 10.1016/j.atherosclerosis.2012.03.012
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- Co-Autor*innen der Med Uni Graz
- Eller Philipp
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- 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens, CD36 - genetics Antigens, CD36 - metabolism
- Apolipoprotein A-I - blood
- Apolipoproteins B - blood
- Atherosclerosis - blood Atherosclerosis - genetics Atherosclerosis - therapy
- Biological Markers - blood
- Cell Line, Tumor -
- Cholesterol Ester Transfer Proteins - metabolism
- Cholesterol Esters - metabolism
- Cholesterol, HDL - blood
- Cholesterol, VLDL - blood
- Disease Models, Animal -
- Genetic Therapy - methods
- Humans -
- Hypercholesterolemia - blood Hypercholesterolemia - complications
- Injections, Intravenous -
- Liver - metabolism
- Male -
- RNA Interference -
- RNA, Small Interfering - administration and dosage RNA, Small Interfering - metabolism
- Rabbits -
- Time Factors -
- Transfection -
- Find related publications in this database (Keywords)
- Gene therapy
- Hypercholesterolemia
- Cholesteryl ester transfer protein
- HDL receptor
- Rabbits