Cycling of apolipoprotein A-I between lipid-associated and lipid-free pools.
It has been shown previously that the reduction in particle size of HDL which follows incubation with the cholesteryl ester transfer protein (CETP) plus very-low-density lipoproteins (VLDL) or low-density lipoproteins (LDL) is accompanied by the dissociation of lipid-free apolipoprotein A-I (apo A-I) from HDL. In the present study, we demonstrate that this dissociation of apo A-I is reversible in a process dependent on the activity of lecithin:cholesterol acyltransferase (LCAT). The lipoprotein fraction (d < 1.21 g/ml) of human plasma was mixed with CETP and incubated under conditions such that the HDL decreased in size and there was a dissociation of about 30% of the apo A-I. Following this incubation, the d < 1.21 g/ml fraction was reisolated, supplemented with lipid-free apo A-I and reincubated in the presence and absence of LCAT, either as a component of lipoprotein-deficient plasma or as purified enzyme. In the absence of LCAT, HDL size did not increase and there was no incorporation of lipid-free apo A-I into the HDL density range. In contrast, when LCAT was present, the particle size of HDL increased and lipid-free apo A-I was incorporated into the HDL such that the HDL apo A-I content was comparable to that of the original, unmodified particles. The incorporation of lipid-free apo A-I into the HDL density range was dependent on both the presence of pre-existing HDL and an increase in their size. Thus, just as a reduction in HDL size is accompanied by the dissociation of lipid-free apo A-I, we have now shown that a subsequent increase in HDL size is accompanied by the reincorporation of lipid-free apo A-I into the particle.
Liang
H Q
HQ
Lipid Research Laboratory, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, Australia.
Rye
K A
KA
Barter
P J
PJ
D016632:Apolipoprotein A-I / Q000097:blood*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D012016:Reference Values; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D002785:Sterol O-Acyltransferase