In vitro transformation of apoA-I-containing lipoprotein subpopulations: role of lecithin:cholesterol acyltransferase and apoB-containing lipoproteins.

Abstract

Two populations of apoA-I-containing lipoproteins are found in plasma: particles with apoA-II [Lp(AI w AII)] and particles without apoA-II [Lp(AI w/o AII)]. Both are heterogeneous in size. However, their size subpopulation distributions differ considerably between healthy subjects and patients with coronary artery diseases. The metabolic basis for such alterations was studied by determining the role of lecithin:cholesterol acyltransferase (LCAT) and apoB-containing lipoproteins (LpB) in the size subpopulation distributions of Lp(AI w AII) and Lp(AI w/o AII). ApoB-free and LCAT-free plasmas, prepared by affinity chromatography, and whole plasma were incubated at 4 degrees C and 37 degrees C for 24 hr. After incubation, Lp(AI w AII) and Lp(AI w/o AII) were isolated by anti-A-II and anti-A-I immunosorbents. Their size subpopulation distributions were studied by nondenaturing gradient polyacrylamide gel electrophoresis. At 4 degrees C most Lp(AI w AII) particles were in the range of 7.0-9.2 nm Stokes diameter. Incubation of plasma at 37 degrees C resulted in an overall enlargement of particles up to 11.2 nm and larger. These particles were enriched with cholesteryl ester and triglyceride and depleted of phospholipids and free cholesterol. Removal of LpB or LCAT from plasma prior to incubation greatly reduced their enlargement. At 4 degrees C, Lp(AI w/o AII) contained mostly particles of 8.5 and 10.1 nm. Incubation at 37 degrees C abolished both subpopulations with the formation of a new subpopulation of 9.2 nm. This transformation was identical in apoB-free plasma but was not seen in LCAT-free plasma. Our study shows that transformation of Lp(AI w AII) requires both LCAT and LpB. However, LpB is not necessary for the transformation of Lp(AI w/o AII) in vitro. The relevance of these in vitro studies to in vivo lipoprotein metabolism was demonstrated in a subject with hepatic triglyceride lipase deficiency.