Scavenger receptor BI (SR-BI) mediates a higher selective cholesteryl ester uptake from LpA-I compared with LpA-I:A-II lipoprotein particles

Abstract

Scavenger receptor class B, type I (SR-BI) mediates the selective uptake of high-density lipoprotein- (HDL-) associated cholesteryl esters (CE), i.e. lipid uptake independent from HDL holo-particle internalisation. This pathway contributes to the HDL-mediated CE delivery to the liver. From human plasma HDL, two major lipoprotein subfractions can be isolated: one contains apolipoprotein (apo) A-I and apo A-II (LpA-I:A-II) as dominant protein components, whereas in the other population apo A-II is absent (LpA-I). In this investigation the role of SR-BI in selective CE uptake from HDL, LpA-I and LpA-I:A-II was explored. HDL 3 ( d=1.125–1.21 g/ml), LpA-I and LpA-I:A-II were isolated from human plasma and radiolabeled in the protein ( 125I) as well as in the CE moiety ([ 3H]). Baby hamster kidney (BHK) cells were stably transfected with the full-length human SR-BI cDNA and these cells demonstrate SR-BI expression in immunoblots. In contrast, no SR-BI protein was detectable in control BHK cells (vector). To investigate lipoprotein uptake, cells incubated (37 °C, 4 h) in medium containing radiolabeled HDL 3, LpA-I or LpA-I:A-II and finally cellular tracer content was determined. For both types of BHK cells, the rate of apparent lipoprotein particle uptake according to the lipid tracer ([ 3H]) was in substantial excess over that due to the protein tracer ( 125I) demonstrating selective CE uptake ([ 3H]– 125I) from HDL 3, LpA-I and LpA-I:A-II. SR-BI expression increased cellular selective CE uptake from labeled HDL 3 up to 24-fold. In BHK cells without SR-BI expression, selective CE uptake was higher from LpA-I compared with LpA-I:A-II. Analogously, in BHK cells with SR-BI expression, the rate of selective CE uptake was higher from LpA-I compared with LpA-I:A-II. In summary, SR-BI significantly increases selective CE uptake from HDL 3, LpA-I and LpA-I:A-II. Concerning HDL subfractions, the rate of SR-BI-mediated selective CE uptake is greater from LpA-I compared with LpA-I:A-II and this result suggests that SR-BI preferentially facilitates the CE transfer from LpA-I lipoprotein particles to cells.