Different reactivities of high density lipoprotein₂ subfractions with hepatic lipase

Human high density lipoproteins₂ (HDL₂) consist of particles that contain both apolipoprotein (apo) A-I and apoA-II (A-I/A-II-HDL₂) and others that contain apoA-I but are devoid of apoA-II (A-I-HDL₂). When postprandial lipemia is pronounced, a fraction of HDL₂ is converted into HDL₃-like particles. These HDL₃ exhibit lower apoA-I/apoA-II ratios than the parent HDL₂, suggesting preferential conversion of A-I/A-II- HDL₂ into HDL₃ (J. Clin. Invest. 1984. 74: 2017-2023). Triglyceride transfer from triglyceride-rich lipoproteins to HDL₂ and subsequent lipolysis by hepatic lipase are thought to mediate the conversion of HDL₂ into HDL₃. To understand why A-I/A-II-HDL₂ are preferentially converted into HDL₃, we separated postprandial HDL₂ into A-I-HDL₂ and A-I/A-II-HDL₂ species by immunoaffinity chromatography using a monoclonal antibody for apoA-II, and determined the ability of HDL₂ species i) to participate in protein-mediated lipid transfer; and ii) to interact with hepatic lipase in vitro. Triglyceride transfer from/to triglyceride-rich lipoproteins was similar for the two HDL₂ species. In contrast, A-I/A-II-HDL₂ were twice as effective as A-I-HDL₂ in liberating hepatic lipase immobilized on HDL₃-Sepharose. Lipolysis of triglycerides by hepatic lipase was 60% higher in postprandial A-I/A-II- HDL₂ than in postprandial A-I-HDL₂. Hydrolysis of phosphatidylcholine by hepatic lipase was threefold higher in A-II-containing HDL₂ when compared with HDL₂ devoid of apoA-II. The different lipolytic rates in HDL₂ subspecies correlated with the size reduction of substrate lipoproteins. Reconstitution of postprandial A-I-HDL₂ with apoA-II enhanced the rate of lipolysis by hepatic lipase to that observed in A- I/A-II-HDL₂. We conclude that it is the interaction with hepatic lipase rather than the rate of triglyceride transfer that results in the preferred conversion of postprandial A-II-containing HDL₂ into HDL₃, and that apoA-II exerts a crucial role in this process.