The removal from plasma of chylomicrons and remnants is reduced in heterozygous familial hypercholesterolemia subjects with identified LDL receptor mutations: study with artificial emulsions

Atherosclerosis. 2012 Mar;221(1):268-74. doi: 10.1016/j.atherosclerosis.2011.12.033. Epub 2011 Dec 29.

Abstract

Chylomicron remnants bind to both their specific receptors (LRP) and to the LDL receptor (LDLR) in the liver. There is controversy whether disturbances of chylomicron metabolism occur in subjects with familial hypercholesterolemia (FH). The aim of this study was to evaluate whether there are defects on the removal from plasma of chylomicrons and their remnants in heterozygous FH patients with determined LDLR mutations. We studied 20 heterozygous FH patients (43.2±12 years old, 60% males) and 50 normolipidemic subjects matched for age and gender. FH subjects were not in use of LDL-lowering drugs for at least 6 weeks. The removal from plasma of chylomicrons and their remnants was measured by isotopic decay after venous injection of a chylomicron-like emulsion radiolabeled with (14)C-cholesteryl ester ((14)C-CE) and (3)H-triolein ((3)H-TO). These track respectively removal from plasma of chylomicrons and remnants and lipolysis. There was a significant reduction in the fractional catabolic rates (FCR in h(-1)) of (14)C-CE in FH in comparison with normolipidemics: 0.048 (1.46.10(-7); 0.57) vs. 0.71(0.049; 1.62), [median (25th-75th percentile)], p=0.003. No differences were found in FCR of (3)H-TO between FH and controls, respectively 1.62 (1.02; 2.331) and 1.914 (1.34; 2.878), p=0.405. In conclusion heterozygous FH subjects had a significant decrease on the removal from plasma of chylomicrons and their remnants compared with normolipidemics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brazil
  • Carbon Radioisotopes
  • Case-Control Studies
  • Chi-Square Distribution
  • Cholesterol Esters / administration & dosage
  • Cholesterol Esters / blood
  • Cholesterol Esters / pharmacokinetics
  • Chylomicron Remnants / blood*
  • Chylomicrons / blood*
  • Emulsions
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote*
  • Humans
  • Hyperlipoproteinemia Type II / blood*
  • Hyperlipoproteinemia Type II / genetics*
  • Injections, Intravenous
  • Lipolysis
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Receptors, LDL / genetics*
  • Triolein / administration & dosage
  • Triolein / pharmacokinetics
  • Tritium

Substances

  • Carbon Radioisotopes
  • Cholesterol Esters
  • Chylomicron Remnants
  • Chylomicrons
  • Emulsions
  • Receptors, LDL
  • Tritium
  • Triolein