Relationship of apolipoprotein(a) isoform size with clearance and production of lipoprotein(a) in a diverse cohort.
Relationship of apolipoprotein(a) isoform size with clearance and production of lipoprotein(a) in a diverse cohort.
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DOI：
10.1016/j.jlr.2023.100336
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发表时间：
2023-03
影响因子：
6.5
通讯作者：
Reyes-Soffer, Gissette
中科院分区：
文献类型：
--
作者：
Matveyenko, Anastasiya;Matienzo, Nelsa;Ginsberg, Henry;Nandakumar, Renu;Seid, Heather;Ramakrishnan, Rajasekhar;Holleran, Steve;Thomas, Tiffany;Reyes-Soffer, Gissette
关键词：
脂蛋白(A)[Lp(A)]有两种主要蛋白质，apoB100和apo(A)。高水平的Lp(A)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中的载脂蛋白(A)亚型，它们的分子质量不同，由Kringle IV类型2重复的数量决定。以前的研究报道了Lp(A)水平和apo(A)亚型大小之间的强烈负相关关系。Lp(A)生产和部分清除的作用以及祖先如何影响这种关系仍然没有完全确定。因此，我们研究了32名未接受降脂治疗的个体的载脂蛋白(A)大小与Lp(A)水平以及载脂蛋白(A)部分清除率(FCR)和产出率(PR)的关系。我们测定了血浆Lp(A)水平和apo(A)异构体大小，并利用这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(R2=0.27；P=0.002)。Wis与apo(A)FCR呈中度正相关(R2=0.10，P=0.08)，与apo(A)PR呈负相关(R2=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(R2=0.24，P=0.03)；控制SRRE不影响WIS与FCR之间的关系。Apo(A)Wis在FCR和PR中都起作用；然而，调整SRRE加强了Wis和PR之间的相关性，暗示了祖先的影响。
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 (R2 = 0.27; P = 0.002). The wIS had a modest positive correlation with apo(a) FCR (R2 = 0.10, P = 0.08) and a negative correlation with apo(a) PR (R2 = 0.11; P = 0.06). The relationship between wIS and PR became significant when we controlled for self-reported race and ethnicity (SRRE) (R2 = 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.
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DOI：
10.1161/01.atv.12.3.302
发表时间：
1992-03-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
KRAFT, HG;SANDHOLZER, C;UTERMANN, G
通讯作者：
UTERMANN, G
影响因子：
15.9
作者：
BOERWINKLE, E;LEFFERT, CC;HOBBS, HH
通讯作者：
HOBBS, HH
影响因子：
15.9
作者：
LACKNER, C;BOERWINKLE, E;HOBBS, HH
通讯作者：
HOBBS, HH
影响因子：
19.6
作者：
Frischmann, M. E.;Kronenberg, F.;Dieplinger, H.
通讯作者：
Dieplinger, H.
影响因子：
13.6
作者：
Doucet, C;Mooser, V;Thillet, J
通讯作者：
Thillet, J