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

• Published in: Journal of lipid research Vol. 40; no. 8; pp. 1506 - 1511
• Main Authors: Frénais, R, Ouguerram, K, Maugeais, C, Marchini, J S, Benlian, P, Bard, J M, Magot, T, Krempf, M
• Format: Journal Article
• Language: English
• Published: United States Elsevier 01.08.1999
• Subjects: Adult; apo AI; Apolipoprotein A-I - metabolism; Apolipoproteins E; Deuterium; Female; Gene Expression Regulation; HDL; Heterozygote; heterozygous familial hypercholesterolemia; Humans; Hyperlipoproteinemia Type II - metabolism; kinetic analysis; Lipoproteins, HDL - metabolism; Male; Middle Aged; Receptors, LDL - genetics; stable isotope
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1016/S0022-2275(20)33394-0

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-(2)H(3)]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 HDL(2) and HDL(3) 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.