Atherosclerosis and Lipoproteins |
From the Department of Cardiovascular Biochemistry (M.N.N., C.J.C., W.L.O., N.E.M.), St Bartholomews and the Royal London School of Medicine and Dentistry, London, UK, and the Department of Surgical Research and Transplantology (W.L.O.), Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Correspondence to Prof Norman E. Miller, Department of Cardiovascular Biochemistry, St Bartholomews and the Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. E-mail n.e.miller{at}mds.qmw.ac.uk
AbstractWhen cultured cells are
exposed to plasma, the initial acceptors of unesterified
cholesterol are small lipid-poor apolipoprotein A-I
(apoA-I)containing high density lipoproteins (HDLs) with pre-ß
electrophoretic mobility. These are converted by
lecithin:cholesterol acyltransferase into larger spheroidal
cholesteryl esterrich HDLs with
mobility. To study the
determinants of the concentration of small pre-ß HDLs in tissue
fluids, we collected prenodal peripheral lymph from 34
fasted normal men. By crossed immunoelectrophoresis, the concentration
of pre-ß HDLs in lymph averaged 20% of that in plasma. On multiple
regression analysis, pre-ß apoA-I concentration in lymph was
directly related to pre-ß apoA-I concentration in plasma and
independently to
apoA-I concentration in lymph. Similar results
were obtained when the same apoA-Icontaining particles were
quantified by size exclusion chromatography. Lymph
pre-ß apoA-I concentration was low in a subject with familial
lecithin:cholesterol acyltransferase deficiency, despite a
normal plasma pre-ß apoA-I concentration, but was normal in a subject
with familial lipoprotein lipase deficiency. These results suggest that
the concentration of small pre-ß HDLs in human tissue fluids is
determined only in part by the transfer of pre-ß HDLs across
capillary endothelium from plasma. Local
production, by remodeling of spheroidal
HDLs in tissue
fluids, may be equally important. Lipolysis of
triglyceride-rich lipoproteins by lipoprotein lipase
appears to have little effect.
Key Words: apoA-I lymph lipoprotein subclasses LCAT deficiency LPL deficiency
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