Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA.
J Lipid Res. 2023 Mar;64(3):100336. doi: 10.1016/j.jlr.2023.100336. Epub 2023 Jan 24.
Lipoprotein(a) [Lp(a)] has two main proteins, apoB100 and apo(a). High levels of Lp(a) confer an increased risk for atherosclerotic cardiovascular disease. Most people have two circulating isoforms of apo(a) differing in their molecular mass, determined by the number of Kringle IV Type 2 repeats. Previous studies report a strong inverse relationship between Lp(a) levels and apo(a) isoform sizes. The roles of Lp(a) production and fractional clearance and how ancestry affects this relationship remain incompletely defined. We therefore examined the relationships of apo(a) size with Lp(a) levels and both apo(a) fractional clearance rates (FCR) and production rates (PR) in 32 individuals not on lipid-lowering treatment. We determined plasma Lp(a) levels and apo(a) isoform sizes, and used the relative expression of the two isoforms to calculate a "weighted isoform size" (wIS). Stable isotope studies were performed, using D3-leucine, to determine the apo(a) FCR and PR. As expected, plasma Lp(a) concentrations were inversely correlated with wIS (R = 0.27; P = 0.002). The wIS had a modest positive correlation with apo(a) FCR (R = 0.10, P = 0.08), and a negative correlation with apo(a) PR (R = 0.11; P = 0.06). The relationship between wIS and PR became significant when we controlled for self-reported race and ethnicity (SRRE) (R = 0.24, P = 0.03); controlling for SRRE did not affect the relationship between wIS and FCR. Apo(a) wIS plays a role in both FCR and PR; however, adjusting for SRRE strengthens the correlation between wIS and PR, suggesting an effect of ancestry.
脂蛋白(a) [Lp(a)] 由两种主要蛋白组成,载脂蛋白 B100 和载脂蛋白(a)。Lp(a) 水平升高会增加动脉粥样硬化性心血管疾病的风险。大多数人有两种循环型载脂蛋白(a)异构体,其分子质量不同,由 Kringle IV 型 2 重复次数决定。先前的研究报告称,Lp(a)水平与载脂蛋白(a)异构体大小之间存在强烈的负相关关系。Lp(a)产生和分数清除率的作用以及遗传背景如何影响这种关系仍未完全定义。因此,我们在 32 名未接受降脂治疗的个体中检查了载脂蛋白(a)大小与 Lp(a)水平以及载脂蛋白(a)分数清除率 (FCR) 和产生率 (PR) 的关系。我们测定了血浆 Lp(a)水平和载脂蛋白(a)异构体大小,并使用两种异构体的相对表达来计算“加权异构体大小”(wIS)。使用 D3-亮氨酸进行稳定同位素研究,以确定载脂蛋白(a) FCR 和 PR。正如预期的那样,血浆 Lp(a)浓度与 wIS 呈负相关 (R = 0.27;P = 0.002)。wIS 与 apo(a) FCR 呈适度正相关 (R = 0.10,P = 0.08),与 apo(a) PR 呈负相关 (R = 0.11;P = 0.06)。当我们控制自我报告的种族和民族 (SRRE) 时,wIS 与 PR 之间的关系变得显著 (R = 0.24,P = 0.03);控制 SRRE 并不影响 wIS 与 FCR 之间的关系。载脂蛋白(a) wIS 同时在 FCR 和 PR 中起作用;然而,调整 SRRE 会增强 wIS 与 PR 之间的相关性,这表明遗传背景的影响。
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