Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on LCAT, PLTP, and CETP in plasma and peripheral lymph in humans.
OBJECTIVE
We have previously shown that intravenous apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) discs increase plasma pre-beta HDL concentration and stimulate reverse cholesterol transport (RCT) in humans. We have now investigated the associated changes in the following 3 HDL components that play key roles in RCT: lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP).


RESULTS
apoA-I/PC discs (40 mg/kg over 4 hours) were infused into 8 healthy men. Samples of blood and prenodal peripheral lymph were collected for 24 to 48 hours. At 12 hours, plasma LCAT concentration had increased by 0.40+/-0.90 mg/L (+7.8%; mean+/-SD; P<0.05), plasma cholesterol esterification rate by 29.0+/-9.0 nmol/mL per h (+69.5%; P<0.01), plasma CETP concentration by 0.5+/-0.2 mg/L (+29.7%; P<0.01), and plasma PLTP activity by 1.45+/-0.67 micromol/mL per h (+23.9%; P<0.01). In contrast, plasma PLTP concentration had decreased by 4.4+/-2.7 mg/L (-44.8%; P<0.01). The changes in PLTP were accompanied by alterations in the relative proportions of large lipoproteins containing inactive PLTP and small particles containing PLTP of high specific activity. No changes were detected in peripheral lymph.


CONCLUSIONS
Nascent HDL secretion may induce changes in PLTP, LCAT, and CETP that promote RCT by catalyzing pre-beta HDL production, cholesterol esterification in HDLs, and cholesteryl ester transfer from HDLs to other lipoproteins.
Kujiraoka
Takeshi
T
Department of Advanced Medical Technology and Development, BML, Inc, 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan.
Nanjee
M Nazeem
MN
Oka
Tomoichiro
T
Ito
Mayumi
M
Nagano
Makoto
M
Cooke
C Justin
CJ
Takahashi
Sadao
S
Olszewski
Waldemar L
WL
Wong
Jinny S
JS
Stepanova
Irina P
IP
Hamilton
Robert L
RL
Egashira
Tohru
T
Hattori
Hiroaki
H
Miller
Norman E
NE
D000328:Adult; D016632:Apolipoprotein A-I / Q000008:administration & dosage* / Q000494:pharmacology*; D001053:Apolipoproteins / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000494:pharmacology; D016503:Drug Delivery Systems; D006023:Glycoproteins; D006801:Humans; D007262:Infusions, Intravenous; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000648:ultrastructure; D008196:Lymph / Q000737:chemistry*; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000378:metabolism; D008854:Microscopy, Electron; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood / Q000378:metabolism; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000494:pharmacology*; D049294:Phospholipid Transfer Proteins
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001798:Blood Proteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D003692:Delayed-Action Preparations; D006023:Glycoproteins; D008055:Lipids; D008074:Lipoproteins; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D049294:Phospholipid Transfer Proteins; D007862:Phosphatidylcholine-Sterol O-Acyltransferase