Advanced glycation end products (AGE) inhibit scavenger receptor class B type I-mediated reverse cholesterol transport: a new crossroad of AGE to cholesterol metabolism.

Abstract

Advanced glycation end products (AGE) -modified proteins behave as active ligands for several receptors belonging to the scavenger receptor family. Scavenger receptor class B type I (SR-BI) was identified as the first high density lipoprotein (HDL) receptor that mediates selective uptake of HDL-cholesteryl esters (HDL-CE). This study investigated whether AGE proteins serve as ligands for SR-BI and affect SR-BI-mediated cholesterol transport using Chinese hamster ovary (CHO) cells overexpressing hamster SR-BI (CHO-SR-BI cells). [125I] AGE-bovine serum albumin (AGE-BSA) underwent active endocytosis and subsequent lysosomal degradation by CHO-SR-BI cells, indicating that SR-BI serves as an AGE receptor. SR-BI-mediated selective uptake of HDL-CE by CHO-SR-BI cells was efficiently inhibited by AGE-BSA although AGE-BSA had no effect on HDL binding to CHO-SR-BI cells. In addition, AGE-BSA significantly inhibited the efflux of [3H] cholesterol from CHO-SR-BI cells to HDL. These findings suggest the possibility that AGE proteins in the circulation interfere with the functions of SR-BI in reverse cholesterol transport by inhibiting the selective uptake of HDL-CE, as well as cholesterol efflux from peripheral cells to HDL, thereby accelerating diabetes-induced atherosclerosis.