title: Lack of evidence for reduced plasma apo B48 catabolism in patients with heterozygous familial hypercholesterolemia carrying the same null LDL receptor gene mutation.
abstract: Increasing evidence suggests that remnants of chylomicrons and very low density lipoprotein (VLDL) also known as triglyceride-rich lipoproteins (TRL) are directly related to the pathogenesis of atherosclerosis. While studies in animals suggest that low density lipoprotein (LDL) receptor deficiency delays clearance of chylomicron remnants, human data supporting this hypothesis are conflicting. The objective of this study was to compare the fractional catabolic rate (FCR) and production rate (PR) of TRL apolipoprotein B48, the principal structural protein of intestinally derived chylomicron remnants, between familial hypercholesterolemic (FH) heterozygotes and non-FH controls. This was achieved by examining the kinetics of TRL apo B48 labelled with a stable isotope (L-(5,5,5-D3)leucine) in five normolipidemic males (age: 24.7 +/- 1.3 years; body mass index (BMI): 23.9 +/- 1.4 kg/m2) and six genetically defined FH heterozygous males (age: 29.7 +/- 9.9 years; (BMI): 22.0 +/- 4.3 kg/m2) carrying the same null LDL receptor gene mutation. All participants were apo E3 homozygotes. During the kinetic study, the subjects consumed 1/30 of their daily food intake every 30 min over a 15 h period. No significant difference was observed between FH heterozygotes and controls for FCR of TRL apo B48 (7.9 +/- 2.1 versus 7.9 +/- 2.6 pools per day, P = 0.99) while the TRL apo B48 pool size (10.5 +/- 5.4 versus 5.7 +/- 2.4 mg, P = 0.03) and PR (1.1 +/- 0.3 versus 0.6 +/- 0.3 mg kg(-1) per day, P = 0.02) were significantly higher among FH than in controls. In conclusion, this study shows no evidence for reduced plasma apo B48 catabolism in patients with heterozygous FH carrying the same null LDL receptor gene mutation and suggests that the plasma levels of intestinally derived TRL are elevated in FH due to an increased production rate.
authors.affiliation: Lipid Research Center, CHUQ Research Center, 2705 Laurier boulevard, S-102, Quebec, Que., Canada G1V 4G2.
authors.forename: André J
authors.initials: AJ
authors.lastname: Tremblay
authors.forename: Benoît
authors.initials: B
authors.lastname: Lamarche
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ruel
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Hogue
authors.forename: Jean
authors.initials: J
authors.lastname: Bergeron
authors.forename: Claude
authors.initials: C
authors.lastname: Gagné
authors.forename: Patrick
authors.initials: P
authors.lastname: Couture
mesh_terms: D000328:Adult; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood*; D053298:Chylomicron Remnants; D002914:Chylomicrons / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics*; D007554:Isotopes; D007930:Leucine; D008297:Male; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D053298:Chylomicron Remnants; D002914:Chylomicrons; D007554:Isotopes; D011973:Receptors, LDL; D007930:Leucine