title: Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans.
abstract: 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.
  
  
  RESULTS
  Four subjects with heterozygous familial hypercholesterolemia w re 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 approximately 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.
authors.affiliation: Center for Metabolism and Endocrinology, Department of Medicine, Novum, Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Eriksson
authors.forename: L A
authors.initials: LA
authors.lastname: Carlson
authors.forename: T A
authors.initials: TA
authors.lastname: Miettinen
authors.forename: B
authors.initials: B
authors.lastname: Angelin
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D001054:Apolipoproteins A / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000188:drug therapy*; D001647:Bile Acids and Salts / Q000032:analysis*; D001692:Biological Transport / Q000187:drug effects; D015415:Biomarkers; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism; D004341:Drug Evaluation; D005243:Feces / Q000737:chemistry*; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D007262:Infusions, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000008:administration & dosage; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013261:Sterols / Q000032:analysis*
chemical_list: D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001647:Bile Acids and Salts; D015415:Biomarkers; D008076:Cholesterol, HDL; D008081:Liposomes; D010743:Phospholipids; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D013261:Sterols; C095606:apolipoprotein A-I Helsinki; C001521:lathosterol; D002784:Cholesterol