CSL112, a Recombinant Apolipoprotein A-I, Enhances Lecithin-Cholesterol Acyltransferase Activity within HDL and Augments Reverse Cholesterol Transport

Although high-density lipoprotein (HDL) cholesterol levels are inversely associated with cardiovascular risk, therapeutic strategies increasingly focus on enhancing reverse cholesterol transport (RCT) and HDL functionality through apolipoprotein A-I (ApoA-I). This study investigated the effects of CSL112 infusion on HDL protein composition, cholesterol esterification rate (CER), and cholesterol efflux capacity (CEC) in patients following acute myocardial infarction. CSL112 infusion led to extensive remodeling of HDL particles, characterized by significant depletion of apolipoproteins A2, B, C, and E, as well as serum amyloids A1 and A4, while markedly enriching ApoA-I, ApoM, and lecithin-cholesterol acyltransferase (LCAT) levels. These proteomic changes were accompanied by increased HDL cholesterol concentrations, elevated CER (reflecting enhanced LCAT activity), and significantly improved CEC, including enhanced hepatic uptake of cholesterol. Overall, CSL112 augmented multiple steps of the RCT pathway, including cholesterol efflux from cells, esterification within HDL, and subsequent transport to the liver. These findings provide mechanistic support for CSL112’s potential to improve HDL function and offer cardiovascular protection in high-risk patients post-myocardial infarction.