Effect of low-density lipoprotein apheresis on kinetics of apolipoprotein B in heterozygous familial hypercholesterolemia

• Published in: The journal of clinical endocrinology and metabolism Vol. 86; no. 4; pp. 1679 - 1686
• Main Authors: MAUGEAIS, Cyrille, OUGUERRAM, Khadija, FRENAIS, Regis, MAUGERE, Pascale, CHARBONNEL, Bernard, MAGOT, Thierry, KREMPF, Michel
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-04-2001
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Apolipoproteins B - blood; Biological and medical sciences; Blood Component Removal; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Case-Control Studies; Female; Heterozygote; Humans; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - genetics; Kinetics; Lipoproteins, LDL - blood; Lipoproteins, VLDL - blood; Male; Medical sciences; Middle Aged; Models, Biological; Reference Values; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; Apheresis; Treatment efficiency; Metabolic diseases; Lipids; Hyperlipoproteinemia; Metabolism; Genetic disease; Apolipoprotein B; Lipoprotein LDL; Hypercholesterolemia; Adult; Kinetics; Dyslipemia
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.86.4.1679

The acute reduction of low-density lipoprotein (LDL) cholesterol obtained by LDL-apheresis allows the role of the high level of circulating LDL on lipoprotein metabolism in heterozygous familial hypercholesterolemia (heterozygous FH) to be addressed. We studied apolipoprotein B (apoB) kinetics in five heterozygous FH patients before and the day after an apheresis treatment using endogenous labeling with [(2)H(3)]leucine. Compared with younger control subjects, heterozygous FH patients before apheresis showed a significant decrease in the fractional catabolic rate of LDL (0.24 +/- 0.08 vs. 0.65 +/- 0.22 day(-1); P < 0.01), and LDL production was increased in heterozygous FH patients (18.9 +/- 7.0 vs. 9.9 +/- 4.2 mg/kg.day; P < 0.05). The modeling of postapheresis apoB kinetics was performed using a nonsteady state condition, taking into account the changing pool size of very low density lipoprotein (VLDL), intermediate density lipoprotein, and LDL apoB. The postapheresis kinetic parameters did not show statistical differences compared with preapheresis parameters in heterozygous FH patients; however, a trend for increases in fractional catabolic rate of LDL (0.24 +/- 0.08 vs. 0.35 +/- 0.09 day(-1); P = 0.067) and the production of VLDL (13.7 +/- 8.3 vs. 21.9 +/- 1.6 mg/kg.day; P = 0.076) was observed. These results suggested that the marked decrease in plasma LDL obtained a short time after LDL-apheresis is able to stimulate LDL receptor activity and VLDL production in heterozygous FH.