4.7 Article

Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a)

Journal

METABOLISM-CLINICAL AND EXPERIMENTAL
Volume 65, Issue 4, Pages 381-390

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2015.10.031

Keywords

Lipoprotein(a); Kinetics; Fed state; Hypertriglyceridemia

Funding

  1. U.S. Department of Agriculture Research Service [53-3K-06]
  2. National Institutes of Health [P50 HL083813-01, HL62705]
  3. Abbott Laboratories
  4. Abbott Park, IL (US.)
  5. Clinical and Translational Research Center of Tufts Medical Center

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Objectives. Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a). Materials and Methods. The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9-124.7 nmol/L]. All subjects received a primed constant infusion of [5,5,5-H-2(3)] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry. Results. Multicompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P = 0.04). The median Lp(a) apo(a) production rate at 0.248 nmol/kg . day(-1) was significantly lower than that of Lp(a) apoB-100 at 0.514 nmol/kg . day(-1) (P = 0.03). Conclusion. Our data indicate that apo(a) has a plasma residence time (11 days) that is more than twice as long as that of apoB-100 (4 days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state. (C) 2016 Elsevier Inc. All rights reserved.

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