CLA-1,the human analogue of mouse SR-BI, mediates the selective uptake of cholesterol esters (CE) from HDL. Although native and modified LDL are ligands for SR-BI, the in vivo physiologic role of CLA-I in apoB-containing lipoprotein (B-Lps) metabolism has not been definitively established. To investigate the in vivo function of CLA-1 in remnant lipoprotein (R-Lp) metabolism, recombinant adenovirus (R-AdV) expressing either control luciferase (Lucif;n=9;2x109 pfu) or CLA-1 (n=6;4x108 pfu), were injected into apoE-deficient (apoE-def) mice with increased apoB-48 containing VLDL,IDL and LDL. A 2-fold increase in hepatic expression of an 82 kDa CLA-1 protein was established by Western analysis using a CLA-1 specific antibody. Following R-AdV (day 4) infusion, apoE-def mice expressing CLA-1 had marked reductions in TC=37%(p<0.00009), PL=23%(p<0.02), CE=39%(p<0.0003), and nonHDL-C=39%(p<0.001),with no change in TG=22%(p<0.15) and HDL-C=16%(p<0.2), when compared to baseline apoE-def mice (mg/dl):TC= 402+/-29, PL= 226+/-17, CE=308?19, nonHDL-C=386+/-29, TG=94+/-10, and HDL-C=16+/-1. FPLC analysis confirmed marked reductions in B-Lps cholesterol whereas densitometric scanning following immunoblotting revealed no changes in the plasma levels of apoA-I and apoB-48 in apoE-def mice expressing CLA-1. Luc expression in apoE-def mice did not alter the lipid profile. Thus, R-AdV-mediated expression of CLA-1 in apoE-def mice decreased TC(37%), PL(23%), CE(39%), and nonHDL-C(39%). Expression of CLA-1 does not alter TG, apoA-I, and apoB-48 plasma levels. These studies provide new in vivo evidence for a role of CLA-1 in mediating the selective uptake of CE from R-Lp. Thus, in lipoprotein metabolism, CLA-1 may function not only as an HDL but also as a B-Lp selective CE uptake receptor.
