Formation of spherical, reconstituted high density lipoproteins containingboth apolipoproteins A-I and A-II is mediated by lecithin : cholesterol acyltransferase
Ma. Clay et al., Formation of spherical, reconstituted high density lipoproteins containingboth apolipoproteins A-I and A-II is mediated by lecithin : cholesterol acyltransferase, J BIOL CHEM, 275(12), 2000, pp. 9019-9025
Previous studies have provided detailed information on the formation of sph
erical high density lipoproteins (HDL) containing apolipoprotein (apo) A-I
but no apoA-II (A-I HDL) by an lecithin:cholesterol acyltransferase (LCAT)-
mediated process. In this study we have investigated the formation of spher
ical HDL containing both apoA-I and apoA-II (A-I/A-II HDL). Incubations wer
e carried out containing discoidal A-I reconstituted HDL (rHDL), discoidal
A-II rHDL, and low density lipoproteins in the absence or presence of LCAT,
After the incubation, the rHDL were reisolated and subjected to immunoaffi
nity chromatography to determine whether A-I/A-II rHDL were formed. In the
absence of LCAT, the majority of the rHDL remained as either A-I rHDL or A-
II rHDL, with only a small amount of A-I/A-II rHDL present. By contrast, wh
en LCAT was present, a substantial proportion of the reisolated rHDL were A
-I/A-II rHDL. The identity of the particles was confirmed using apoA-I rock
et electrophoresis, The formation of the A-U A-LI rHDL was influenced by th
e relative concentrations of the precursor discoidal A-I and A-II rHDL, The
A-U A-II rHDL included several populations of HDL-sized particles; the pre
dominant population having a Stokes' diameter of 9.9 nm, The particles were
spherical in shape and had an electrophoretic mobility slightly slower tha
n that of the alpha-migrating HDL in human plasma. The apoA-I:apoA-II molar
ratio of the A-I/A-II rHDL was 0,7:1, Their major lipid constituents were
phospholipids, unesterified cholesterol, and cholesteryl esters, The result
s presented are consistent with LCAT promoting fusion of the A-I rHDL and A
-II rHDL to form spherical A-YA-II rHDL, We suggest that this process may b
e an important source of A-YA-II HDL in human plasma.