In vivo stable-isotope kinetic study suggests intracellular assembly of lipoprotein(a)

被引：53

作者：

Frischmann, Michael E. ^{[1
]}

Ikewaki, Katsunori ^{[2
]}

Trenkwalder, Evi ^{[1
]}

Lamina, Claudia ^{[1
]}

Dieplinger, Benjamin

Soufi, Muhidien ^{[3
]}

Schweer, Horst ^{[4
]}

Schaefer, Juergen R. ^{[3
]}

Koenig, Paul ^{[5
]}

Kronenberg, Florian ^{[1
]}

Dieplinger, Hans ^{[1
]}

机构：

[1] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria

[2] Natl Def Med Coll, Dept Internal Med, Div Antiaging, Tokorozawa, Saitama 359, Japan

[3] Univ Marburg, Dept Internal Med, D-35032 Marburg, Germany

[4] Univ Marburg, Childrens Hosp, D-35032 Marburg, Germany

[5] Innsbruck Med Univ, Univ Clin Internal Med 4, Dept Nephrol & Hypertensiol, A-6020 Innsbruck, Austria

来源：

ATHEROSCLEROSIS | 2012年 / 225卷 / 02期

基金：

奥地利科学基金会;

关键词：

In vivo kinetics; Stable isotopes; Lp(a) assembly; HMW apo(a) isoforms; LMW apo(a) isoforms; APOLIPOPROTEIN-B; HUMAN HEPATOCYTES; METABOLISM; DISEASE; APO(A); LP(A); GENE; IDENTIFICATION; CLEARANCE; PHENOTYPE;

D O I：

10.1016/j.atherosclerosis.2012.09.031

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: Lipoprotein(a) [Lp(a)] consists of apolipoprotein B-100 (apoB-100) as part of an LDL-like particle and the covalently linked glycoprotein apolipoprotein(a) [apo(a)]. Detailed mechanisms of its biosynthesis, assembly, secretion and catabolism are still poorly understood. To address the Lp(a) assembly mechanism, we studied the in vivo kinetics of apo(a) and apoB-100 from Lp(a) and LDL apoB-100 in nine healthy probands using stable-isotope methodology. Methods: The level of isotope enrichment was used to calculate the fractional synthesis rate (FSR), production rate (PR) and retention time (RT) using SAAMII software and multicompartmental modeling. Results: We observed a similar mean PR for apo(a) (1.15 nmol/kg/d) and apoB-100 (1.31 nmol/kg/d) from Lp(a), which differed significantly from the PR for apoB-100 from LDL (32.6 nmol/kg/d). Accordingly, mean FSR and RT values for Lp(a)-apo(a) were similar to those of Lp(a)-apoB and different from those for LDL-apoB. Conclusion: Two different kinetic apoB pools within Lp(a) and LDL suggest intracellular Lp(a) assembly from apo(a) and newly synthesized LDL. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

引用

页码：322 / 327

页数：6

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