title: Increased plasma levels of LDL cholesterol in rabbits after adenoviral overexpression of human scavenger receptor class B type I.
abstract: Scavenger receptor class B type I (SR-BI), a CD36 family member, plays a key role in high-density lipoprotein (HDL) metabolism, reverse cholesterol transport, and whole body cholesterol homeostasis, and is shown to be involved in the development of atherosclerosis in mice. In this report, we describe the effects of the adenoviral overexpression of human SR-BI (hSR-BI) in New Zealand White (NZW) rabbits, a wild-type animal model that expresses cholesteryl ester transfer protein (CETP) in plasma, displays a manlike lipoprotein profile, and is susceptible to atherosclerosis. A total of 1x10(12) adenoviral particles containing either hSR-BI or lacZ complementary deoxyribonucleic acid (control) were infused into the ear vein of NZW rabbits. Transgene expression was ascertained by TaqMan Real Time polymerase chain reaction measurements. Rabbits infected with Ad/hSR-BI (adenoviral plasmids containing hSR-BI) showed a faster clearance of administered [3H]HDL cholesterol and significantly decreased apolipoprotein (apo) A-I levels when compared to control rabbits, respectively. Interestingly, we found markedly increased levels of low-density lipoprotein (LDL) cholesterol exclusively in SR-BI-overexpressing rabbits. These changes were not accompanied by alterations in LDL receptor expression but by increased levels of CE transfer in these animals. By lowering HDL cholesterol and increasing plasma apoB-containing lipoprotein levels, the overexpression of SR-BI leads to a lipoprotein pattern, which is believed to enhance the development of atherosclerosis. The role of SR-BI in lipoprotein metabolism and atherogenesis in rabbits--a CETP-expressing animal model displaying a manlike lipoprotein profile--may therefore be different from the one found in rodents.
authors.affiliation: Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.
authors.forename: Ivan
authors.initials: I
authors.lastname: Tancevski
authors.forename: Sasa
authors.initials: S
authors.lastname: Frank
authors.forename: Petra
authors.initials: P
authors.lastname: Massoner
authors.forename: Ursula
authors.initials: U
authors.lastname: Stanzl
authors.forename: Wilfried
authors.initials: W
authors.lastname: Schgoer
authors.forename: Andreas
authors.initials: A
authors.lastname: Wehinger
authors.forename: Catherine
authors.initials: C
authors.lastname: Fievet
authors.forename: Philipp
authors.initials: P
authors.lastname: Eller
authors.forename: Josef R
authors.initials: JR
authors.lastname: Patsch
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritsch
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood* / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D011817:Rabbits; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D019076:Transgenes; D015854:Up-Regulation
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B