Scavenger receptor BI mediates the selective uptake of oxidized cholesterol esters by rat liver

High density lipoprotein (HDL) can protect low density lipoprotein (LDL) ag ainst oxidation, Oxidized cholesterol esters from LDL can be transferred to HDL and efficiently and selectively removed from the blood circulation by the liver and adrenal in vivo. In the present study, we investigated whethe r scavenger receptor BI (SR-BI) is responsible for this process. At 30 min after injection, the selective uptake of oxidized cholesterol esters from H DL for liver and adrenal was 2.3- and 2.6-fold higher, respectively, than f or native cholesterol esters, whereas other tissues showed no significant d ifference. The selective uptake of oxidized cholesterol esters from HDL by isolated liver parenchymal cells could be blocked for 75% by oxidized LDL a nd for 50% by phosphatidylserine liposomes, both of which are known substra tes of SR-BI, In vivo uptake of oxidized cholesterol esters from HDL by parenchymal cells decreased by 64 and 81% when rats were treated with estradiol and a high c holesterol diet, respectively, whereas Kupffer cells showed 660 and 475% in creases, respectively. These contrasting changes in oxidized cholesterol es ter uptake were accompanied by similar contrasting changes in SR-BI express ion of parenchymal and Kupffer cells. The rates of SR-BI-mediated selective uptake of oxidized and native cholesterol esters were analyzed in SR-BI-tr ansfected Chinese hamster ovary cells. SR-BI-mediated selective uptake was 3.4-fold higher for oxidized than for native cholesterol esters (30 min of incubation). It is concluded that in addition to the selective uptake of na tive cholesterol esters, SR-BI is responsible for the highly efficient Sele ctive uptake of oxidized cholesterol esters from HDL and thus forms an esse ntial mediator in the HDL-associated protection system for atherogenic oxid ized cholesterol esters.