Apolipoprotein A-I kinetics in heterozygous familial hypercholesterolemia: a stable isotope study.
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.
Frénais
R
R
Centre de Recherche en Nutrition Humaine, Groupe Métabolisme, Hôtel Dieu, Nantes, France.
Ouguerram
K
K
Maugeais
C
C
Marchini
J S
JS
Benlian
P
P
Bard
J M
JM
Magot
T
T
Krempf
M
M
D000328:Adult; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001057:Apolipoproteins E; D003903:Deuterium; D005260:Female; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000235:genetics
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D011973:Receptors, LDL; D003903:Deuterium