ApoA-I Infusion Therapies Following Acute Coronary Syndrome: Past, Present, and Future

AbstractPurpose of ReviewThe elevated adverse cardiovascular event rate among patients with low high-density lipoprotein cholesterol (HDL-C) formed the basis for the hypothesis that elevating HDL-C would reduce those events. Attempts to raise endogenous HDL-C levels, however, have consistently failed to show improvements in cardiovascular outcomes. However, steady-state HDL-C concentration does not reflect the function of this complex family of particles. Indeed, HDL functions correlate only weakly with serum HDL-C concentration. Thus, the field has pivoted from simply raising the quantity of HDL-C to a focus on improving the putative anti-atherosclerotic functions of HDL particles. Such functions include the ability of HDL to promote the efflux of cholesterol from cholesterol-laden macrophages. Apolipoprotein A-I (apoA-I), the signature apoprotein of HDL, may facilitate the removal of cholesterol from atherosclerotic plaque, reduce the lesional lipid content and might thus stabilize vulnerable plaques, thereby reducing the risk of cardiac events. Infusion of preparations of apoA-I may improve cholesterol efflux capacity (CEC). This review summarizes the development of apoA-I therapies, compares their structural and functional properties and discusses the findings of previous studies including their limitations, and how CSL112, currently being tested in a phase III trial, may overcome these challenges.Recent FindingsThree major ApoA-I-based approaches (MDCO-216, CER-001, and ...
Source: Current Atherosclerosis Reports - Category: Cardiology Source Type: research