Abstract 15370: Mechanism of High Density Lipoprotein Remodeling Induced by CSL112

Introduction: CSL112 is apolipoprotein A-I (apoA[[Unable to Display Character: ‐]]I) purified from human plasma and reconstituted with phosphatidylcholine to form lipoprotein particles suitable for infusion. This formulation is designed to optimize cholesterol efflux by the ATP-binding cassette A1 (ABCA1) transporter present in macrophages of atherosclerotic plaque. We have recently demonstrated that infusion of CSL112 into humans dramatically raises the ability of plasma to mediate ABCA1-dependent cholesterol efflux and this strong elevation was accompanied by a very large (>30-fold) increase in plasma levels of lipid-poor apoA-I (Pre-Beta1 high density lipoprotein (HDL)), the preferred substrate for ABCA1. In this study we investigated the origin of lipid-poor apoA-I produced upon incubation of CSL112 with human plasma ex vivo. Methods and Results: CSL112 was incubated with human plasma or purified HDL for 1 h at 37°C. HDL particle size distribution was assessed by native gel electrophoresis follo...