School of Biomedical Sciences, University of Western Australia, Perth, Australia; School of Medicine, University of Western Australia, Perth, Australia.
School of Biomedical Sciences, University of Western Australia, Perth, Australia.
Metabolism. 2019 Jul;96:8-11. doi: 10.1016/j.metabol.2019.04.010. Epub 2019 Apr 14.
CONTEXT: Lipoprotein(a) [Lp(a)] is a highly atherogenic lipoprotein characterized by apolipoprotein(a) [apo(a)] covalently bounded to apoB-100 (apoB). However, the metabolism of apo(a) and apoB within plasma Lp(a) particles in patients on statins remains unclear. METHODS: The kinetics of Lp(a)-apo(a) and Lp(a)-apoB were determined in 20 patients with elevated Lp(a) (≥0.8 g/L; n = 10) and normal Lp(a) (≤0.3 g/L; n = 10) using stable isotope techniques and compartmental modeling. Plasma apo(a) concentration was measured using liquid chromatography-mass spectrometry. All patients were on statin therapy and were studied in the fasting state. RESULTS: The fractional catabolic rate (FCR) of Lp(a)-apo(a) was not significantly different from that of Lp(a)-apoB in statin-treated patients with elevated or normal Lp(a) (P > 0.05 in both). Lp(a)-apo(a) FCR was significantly correlated with Lp(a)-apoB in patients with elevated and normal Lp(a) concentrations (r = 0.970 and r = 0.979, respectively; all P < 0.001) with Lin's concordance test showing substantial agreement between the FCRs of Lp(a)-apo(a) and Lp(a)-apoB in patients with elevated and normal Lp(a) concentrations (r = 0.978 and r = 0.966, respectively). CONCLUSION: Our data indicate that the apo(a) and apoB proteins within Lp(a) particles have similar FCR and are therefore tightly coupled as an Lp(a) holoparticle in statin-treated patients with elevated and normal Lp(a) concentrations.
背景:脂蛋白(a) [Lp(a)] 是一种高度致动脉粥样硬化的脂蛋白,其特征是载脂蛋白(a) [apo(a)] 与载脂蛋白 B-100 (apoB) 共价结合。然而,在接受他汀类药物治疗的患者中,血浆 Lp(a) 颗粒内的 apo(a) 和 apoB 的代谢仍不清楚。
方法:使用稳定同位素技术和房室模型,在 20 名 Lp(a)升高(≥0.8 g/L;n=10)和正常(≤0.3 g/L;n=10)的患者中确定 Lp(a)-apo(a) 和 Lp(a)-apoB 的动力学。使用液相色谱-质谱法测量血浆 apo(a)浓度。所有患者均接受他汀类药物治疗,并在禁食状态下进行研究。
结果:在 Lp(a)升高或正常的他汀类药物治疗患者中,Lp(a)-apo(a) 的分解代谢率(FCR)与 Lp(a)-apoB 无显著差异(均 P>0.05)。Lp(a)-apo(a) FCR 与 Lp(a)升高和正常浓度的患者的 Lp(a)-apoB 显著相关(r=0.970 和 r=0.979,均 P<0.001),Lin 一致性检验显示,在 Lp(a)升高和正常浓度的患者中,Lp(a)-apo(a) 和 Lp(a)-apoB 的 FCR 之间存在高度一致性(r=0.978 和 r=0.966,分别)。
结论:我们的数据表明,Lp(a)颗粒内的 apo(a)和 apoB 蛋白具有相似的 FCR,因此在 Lp(a)升高和正常浓度的他汀类药物治疗患者中,它们作为 Lp(a)完整颗粒紧密结合。
J Clin Endocrinol Metab. 2019-12-1
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