Acrolein-conjugated low-density lipoprotein induces macrophage foam cell formation

Abstract

ObjectiveAcrolein-conjugated lysine residues in proteins are present in human atherosclerotic lesions, and are detected in human low-density lipoprotein (LDL). These findings suggest that acrolein may contribute to macrophage foam cell formation and atherogenesis through modification of LDL. The purpose of this study is to determine whether acrolein-conjugated LDL (Acro-LDL) induces macrophage conversion to form foam cells. MethodsAcro-LDL was prepared by incubation of LDL with acrolein. Characteristics of Acro-LDL were examined by agarose gel electrophoresis and western blotting. Cholesterol contents of THP-1 macrophages incubated with Acro-LDL were determined by enzymatic method. Pathway of Acro-LDL uptake by THP-1 macrophages was determined using neutralizing antibody against scavenger receptors. Delivery of Acro-LDL into lysosome and formation of lipid droplet by incubation with Acro-LDL were demonstrated by confocal microscopy. ResultsThe mobility of Acro-LDL determined by agarose gel electrophoresis was increased by modification with acrolein, and the shift of mobility was dependent on the concentration of acrolein. Acrolein interacted with apolipoprotein B in LDL and Acro-LDL uptake by THP-1 macrophage was a more effective inducer of cholesterol accumulation than oxidized LDL uptake. Acro-LDL uptake was mediated by scavenger receptor class A type 1 (SR-A1), but not by CD36. As a result of Acro-LDL uptake, cholesterol ester accumulated in lipid droplets of macrophages, converting them to foam cells. ConclusionsThe results show that Acro-LDL uptake via SR-A1 receptors can mediate macrophage foam cell formation.