Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:979-989
© 1999 American Heart Association, Inc.
Original Contributions |
Acute Effects of Intravenous Infusion of ApoA1/Phosphatidylcholine Discs on Plasma Lipoproteins in Humans
From the Department of Cardiovascular Biochemistry, St Bartholomew's and the Royal London School of Medicine and Dentistry (M.N.N., N.E.M.), London, UK; and ZLB Central Laboratory, Blood Transfusion Service SRC (J.E.D., P.G.L.), Bern, Switzerland.
Correspondence to Prof Norman E. Miller, Department of Cardiovascular Biochemistry, St Bartholomew's and the Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK.
Abstract—To investigate
the metabolism of nascent HDLs, apoA1/phosphatidylcholine
(apoA1/PC) discs were infused IV over 4 hours into 7 healthy men.
Plasma total apoA1 and phospholipid (PL) concentrations increased
during the infusions. The rise in plasma apoA1 was greatest in small
preß-migrating particles not present in the infusate. Total HDL
unesterified cholesterol (UC) also increased
simultaneously. After stopping the infusion, the
concentrations of apoA1, PL, HDL UC, and small preß HDLs decreased,
whereas those of HDL cholesteryl ester (CE) and large 
-migrating
apoA1 containing HDLs increased. ApoB-containing lipoproteins became
enriched in CEs. Addition of apoA1/PC discs to whole blood at 37°C in
vitro also generated small preß HDLs, but did not augment the
transfer of UC from erythrocytes to plasma. We conclude that the disc
infusions increased the intravascular production of small
preß HDLs in vivo, and that this was associated with an increase in
the efflux and esterification of UC derived from fixed tissues. The
extent to which the increase in tissue cholesterol efflux
was dependent on that in preß HDL production could not be
determined. Infusion of discs also reduced the plasma apoB and apoA2
concentrations, and increased plasma triglycerides and
apoC3. Thus, nascent HDL secretion may have a significant impact on
preß HDL production, reverse cholesterol
transport and lipoprotein metabolism in humans.
Key Words: apolipoprotein A1 • cholesterol • HDLs • lecithin • phosphatidylcholine
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