Apolipoprotein A-I kinetics in heterozygous familial hypercholesterolemia: a stable isotope study

Abstract

Heterozygous familial hypercholesterolemia (FH) is associated with a moderate decrease of plasma apoA-I and HDL-cholesterol levels. The aim of the study was to test the hypothesis that these abnormalities were related to an increase of HDL-apoA-I fractional catabolic rate (FCR). We performed a 14-h infusion of [5,5,5-2H3]leucine in seven control subjects and seven heterozygous FH patients (plasma total cholesterol 422 ± 27 vs. 186 ± 42 mg/dL, P < 0.001, respectively). Plasma apoA-I concentration was not changed in FH compared to controls (respectively 115 ± 18 vs. 122 ± 15 mg/dL, NS), and HDL-cholesterol level was decreased (37 ± 7 vs. 46 ± 19 mg/dL, NS). Kinetics of HDL metabolism were modeled as a single compartment as no differences were observed between HDL2 and HDL3 subclasses. Both mean apoA-I FCR and absolute production rate (APR) were increased in FH (respectively, 0.36 ± 0.14 vs. 0.22 ± 0.05 pool/d, P < 0.05, and 18.0 ± 7.7 and 11.2 ± 2.3 mg/kg/d, P < 0.05). Higher HDL-triglyceride and HDL-apoE levels were observed in patients with heterozygous FH. (Respectively 19 ± 8 vs. 8 ± 3 mg/dL, P < 0.05, and 5.3 ± 0.8 vs. 3.7 ± 0.9 mg/dL, P < 0.05). We conclude that the catabolism of HDL-apoA-I is increased in heterozygous FH patients. However, plasma apoA-I concentration was maintained because of an increased HDL-apoA-I production rate.—Frénais, R., K. Ouguerram, C. Maugeais, J. S. Marchini, P. Benlian, J. M. Bard, T. Magot, and M. Krempf. Apolipoprotein A-I kinetics in heterozygous familial hypercholesterolemia: a stable isotope study. J. Lipid Res. 1999. 40: 1506–1511.

Keywords

• heterozygous familial hypercholesterolemia
• stable isotope
• kinetic analysis
• apo AI
• HDL