title: The beta very low density lipoprotein present in hepatic lipase deficiency competitively inhibits low density lipoprotein binding to fibroblasts and stimulates fibroblast acyl-CoA:cholesterol acyltransferase.
abstract: Beta very low density lipoprotein (VLDL) was isolated from a patient with hepatic lipase deficiency. The particles were found to contain apolipoprotein B-100 (apoB) and apolipoprotein E (apoE) and were rich in cholesterol and cholesteryl ester relative to VLDL with pre beta electrophoretic mobility. These particles were active in displacing human low density lipoprotein (LDL) from the fibroblast apoB,E receptor and produced a marked stimulation of acyl-CoA:cholesterol acyltransferase. Treatment of intact beta-VLDL with trypsin abolished its ability to displace LDL from fibroblasts. Incubation of trypsin treated beta-VLDL with fibroblasts resulted in a significant stimulation of acyl-CoA:cholesterol acyltransferase activity. beta-VLDL isolated from a patient with Type III hyperlipoproteinemia and an apoE2/E2 phenotype had a higher cholesteryl ester/triglyceride ratio than the beta-VLDL of hepatic lipase deficiency and contained apoB48. It displaced LDL from fibroblasts to a small but significant extent. The Type III beta-VLDL stimulated acyl-CoA:cholesterol acyltransferase to a level similar to that of trypsin-treated beta-VLDL isolated from the hepatic lipase-deficient patient. These results demonstrate that the cholesterol-rich beta-VLDL particles present in patients with hepatic lipase deficiency are capable of interacting with fibroblasts via the apoB,E receptor and that this interaction is completely due to trypsin-sensitive components of the beta-VLDL. These particles were very effective in stimulating fibroblast acyl-CoA:cholesterol acyltransferase. This stimulation was due to both trypsin-sensitive and trypsin-insensitive components.
authors.affiliation: Department of Medicine, University of Toronto, Canada.
authors.forename: P W
authors.initials: PW
authors.lastname: Connelly
authors.forename: S
authors.initials: S
authors.lastname: Ranganathan
authors.forename: G F
authors.initials: GF
authors.lastname: Maguire
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: J J
authors.initials: JJ
authors.lastname: Myher
authors.forename: B A
authors.initials: BA
authors.lastname: Kottke
authors.forename: A
authors.initials: A
authors.lastname: Kuksis
authors.forename: J A
authors.initials: JA
authors.lastname: Little
mesh_terms: D001053:Apolipoproteins / Q000097:blood; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008049:Lipase / Q000172:deficiency*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000302:isolation & purification; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000378:metabolism*; D012016:Reference Values; D012867:Skin / Q000378:metabolism
chemical_list: D001053:Apolipoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D008049:Lipase