AHA: Infusion of apoA Induces Reverse Cholesterol Transport
(HealthDay News) – Infusion of CSL112 (apolipoprotein A-1 [apoA-1]), the active protein of high-density lipoprotein (HDL), induces key biomarkers in the initial steps of reverse cholesterol transport in healthy individuals.
Andreas Gille, MD, PhD, from CSL Limited in Parkville, Australia, and colleagues examined markers of cholesterol movement following a single infusion of CSL112 (5–135mg/kg) in 57 healthy subjects.
The researchers found that infusion of CSL112 induced a dose-proportional elevation in apoA-1 and alterations to key biomarkers of the early steps in reverse cholesterol transport, including formation of PreBeta1-HDL; increase in global cholesterol efflux capacity from macrophages; movement of free cholesterol to HDL in plasma; increase in HDL-cholesterol; and increase in lecithin-cholesterol acyltransferase activity reflected by a time-dependent change of the ratio of free to esterified cholesterol. The changes occurred in a dose- and time-dependent manner and persisted for at least 72 hours following 40mg/kg and higher-dose infusions of CSL112. There were immediate increases of several-fold above baseline in PreBeta1-HDL and global cholesterol efflux, which reached maximums of 3,600 and 270%, respectively. At the 135mg/kg dose level there was no evidence indicating saturation of the effects of CSL112 on biomarkers, with the exception of PreBeta1-HDL. For apoB, non-HDL cholesterol, and non-HDL triglyceride there were no changes associated with CSL112.
"Overall, CSL112 behaved as well or better than we expected and all the changes are consistent with the desired elevation in reverse cholesterol transport activity," Gille said in a statement. "We did not observe any unfavorable changes in the low-density lipoprotein or 'bad' cholesterol-related biomarkers tested."
The study authors are all employees of CSL Limited, which funded the study.