Cholesterol efflux from fibroblasts to discoidal lipoproteins with apolipoprotein A-I (LpA-I) increases with particle size but cholesterol transfer from LpA-I to lipoproteins decreases with size
To understand the role of different discoidal lipoproteins in cellular cholesterol efflux, defined discoidal lipoproteins containing 2, 3, or 4 apolipoproteins (apo) A-I per particle (Lp2A-I, Lp3A-I, and Lp4A-I) were prepared from mixtures of apoA-I and phospholipids with or without cholesterol. Each particle had a slow pre beta migration on agarose gel electrophoresis which further decreased as the number of apoA-I increased. Incubation of cholesterol-labeled human fibroblasts with the different LpA-I at an equimolar concentration in apoA-I showed that the best acceptors of cellular cholesterol were Lp4A-I, followed by Lp3A-I and Lp2A-I. Cholesterol efflux to these particles was positively correlated to the number of apoA-I, to the ratio of phospholipids to apoA-I, and to the size of particles, three interrelated parameters. To follow the subsequent movement of cellular cholesterol after it became associated with LpA-I, cholesterol- and apoA-I-labeled LpA-I were incubated with plasma which resulted in parallel modifications of each labels electrophoretic migration with time. However, [3H]cholesterol-labeled LpA-I transferred from pre beta to alpha migration with a precursor-product relationship while 125I-LpA-I progressively shifted from pre beta to alpha migration. The change in electrophoretic migration of 125I-LpA-I is independent of cholesterol and appears related only to a modification of apoA-I charge. Lp2A-I was fastest in changing its electrophoretic migration to alpha, followed by Lp3A-I and then Lp4A-I.(ABSTRACT TRUNCATED AT 250 WORDS)