on July 31, 2003
Published online before print July 31, 2003, doi: 10.1161/01.ATV.0000089328.23279.3F
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Submitted on January 27, 2003
Accepted on July 10, 2003
Effects of Intravenous Apolipoprotein A-I/Phosphatidylcholine Discs on LCAT, PLTP, and CETP in Plasma and Peripheral Lymph in Humans
Takeshi Kujiraoka ;
From the Department of Advanced Medical Technology and Development (T.K., T.O., M.I., M.N., T.E., H.H.), BML Inc, Saitama, Japan; Department of Cardiovascular Biochemistry (M.N.N., C.J.C., I.P.S., N.E.M.), St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK; Third Department of Internal Medicine (S.T.), Fukui Medical University, Fukui, Japan; Medical Research Center (W.L.O.), Polish Academy of Sciences, Warsaw, Poland; Cardiovascular Research Institute and Department of Anatomy (J.S.W., R.L.H.), University of California, San Francisco, Calif.
* To whom correspondence should be addressed. E-mail: hhiro{at}bml.co.jp.
Objective--We have previously shown that intravenous apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) discs increase plasma pre-
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).
Methods and 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 µmol/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- HDL production, cholesterol esterification in HDLs, and cholesteryl ester transfer from HDLs to other lipoproteins.
Key words: apolipoprotein A-I • phospholipid transfer protein • lecithin • cholesterol acyltransferase • cholesteryl ester transfer protein
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