Behavior of human apolipoprotein A-I: phospholipid and apoHDL:phospholipid complexes in vitro and after injection into rabbits.
Apolipoprotein A-I was purified from human high density lipoprotein and complexed with polyunsaturated phosphatidylcholine (PC) in deoxycholate (Lipostabil); the bile salt was removed subsequently by dialysis. The behavior of the resultant apoA-I/PC complexes was compared with that of Lipostabil in vitro and after injection into rabbits. In vivo apoA-I/PC complexes had the density of HDL throughout but had both alpha and pre beta electrophoretic mobility, the latter probably reflecting dissociation of apoA-I from PC. Lipostabil initially behaved like LDL but gradually acquired the density of HDL after incubation with plasma and in vivo. Both preparations increased plasma total phospholipids in normolipidemic rabbits to a similar extent, but, increments in HDL phospholipid were greater after apoA-I/PC complexes were injected. ApoHDL/PC complexes, prepared in a similar manner, appeared to promote efflux of cholesterol from perfused rabbit aortas in the presence of lecithin:cholesterol acyltransferase (LCAT) activity, consistent with a stimulatory effect on cholesterol mobilization. Injection of apoHDL/PC complexes into hyperlipidemic rabbits decreased plasma cholesterol but increased HDL cholesterol, whereas Lipostabil decreased both. These findings suggest that human apoA-I/PC complexes resemble HDL in their behavior more closely than does Lipostabil, and show that both types of liposome undergo modification upon interaction with plasma. It remains to be shown whether they possess any therapeutic potential.
Koizumi
J
J
MRC Lipoprotein Team, Hammersmith Hospital, London, U.K.
Kano
M
M
Okabayashi
K
K
Jadhav
A
A
Thompson
G R
GR
D000818:Animals; D001011:Aorta / Q000378:metabolism; D016632:Apolipoprotein A-I; D001053:Apolipoproteins / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001054:Apolipoproteins A / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002499:Centrifugation, Density Gradient; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D004586:Electrophoresis / Q000379:methods; D006579:Heterozygote; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics; D007120:Immunochemistry; D007262:Infusions, Intravenous; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D010743:Phospholipids / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D011817:Rabbits
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001054:Apolipoproteins A; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D010713:Phosphatidylcholines; D010743:Phospholipids; C005152:lipostabil