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(Circulation. 1999;100:594-598.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Stimulation of Fecal Steroid Excretion After Infusion of Recombinant Proapolipoprotein A-I
Potential Reverse Cholesterol Transport in Humans
From the Center for Metabolism and Endocrinology, Department of Medicine, and the Center for Nutrition and Toxicology, Novum, Karolinska Institute at Huddinge University Hospital, Huddinge (M.E., B.A.); King Gustaf V Research Institute, Karolinska Hospital, Stockholm (L.A.C.); and the Department of Medicine, University of Helsinki (T.A.M.).
Correspondence to Dr Bo Angelin, CME M63, Huddinge University Hospital, S-141 86 Huddinge, Sweden. E-mail bo.angelin{at}medhs.ki.se
Background—Apolipoprotein (apo) A-I is the major protein component of HDL, a cholesterol transport particle that protects against atherosclerosis. Apo A-I is believed to promote reverse cholesterol transport, transferring cholesterol from peripheral cells to the liver for subsequent elimination. To test this hypothesis in humans, we measured fecal steroid excretion before and after the intravenous infusion of human proapo A-I (precursor of apo A-I) liposome complexes.
Methods and Results—Four subjects with heterozygous familial
hypercholesterolemia were studied under
standardized conditions. The fecal excretion of bile acids and neutral
sterols was determined for 9 days before and 9 days after an
intravenous infusion of recombinant human proapo A-I (4 g
protein) liposome complexes. Plasma apoA-I and HDL
cholesterol levels increased transiently (mean peak
concentrations were 64% and 35% above baseline, respectively) during
the first 24 hours. Mean lipoprotein lipid and apolipoprotein levels
were not different during the 2 collecting periods, however. Serum
lathosterol, a precursor of cholesterol whose concentration
reflects the rate of cholesterol synthesis in vivo, was
also unchanged. The fecal excretion of cholesterol (neutral
sterols and bile acids) increased in all subjects (mean increase, +39%
and +30%, respectively), corresponding to the removal of 
500 mg/d
excess cholesterol after infusion. Control infusions with
only liposomes in 2 of the patients did not influence lipoprotein
pattern or cholesterol excretion.
Conclusions—Infusion of proapoA-I liposomes in humans promotes net cholesterol excretion from the body, implying a stimulation of reverse cholesterol transport. This mechanism may prove useful in the treatment of atherosclerosis.
Key Words: apolipoproteins • atherosclerosis • cholesterol • lipoproteins • metabolism
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