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脂蛋白(a)通过其氧化磷脂，经清道夫受体-B1上调肝细胞中的ABCA1。

Lipoprotein (a) upregulates ABCA1 in liver cells via scavenger receptor-B1 through its oxidized phospholipids.

作者信息

Sharma Monika, Von Zychlinski-Kleffmann Anne, Porteous Carolyn M, Jones Gregory T, Williams Michael J A, McCormick Sally P A

机构信息

Department of Biochemistry, University of Otago, Dunedin, New Zealand.

Departments of Surgical Sciences University of Otago, Dunedin, New Zealand.

出版信息

J Lipid Res. 2015 Jul;56(7):1318-28. doi: 10.1194/jlr.M056150. Epub 2015 Apr 6.

DOI:10.1194/jlr.M056150
PMID:25852127
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4479336/
Abstract

Elevated levels of lipoprotein (a) [Lp(a)] are a well-established risk factor for developing CVD. While Lp(a) levels are thought to be independent of other plasma lipoproteins, some trials have reported a positive association between Lp(a) and HDL. Whether Lp(a) has a direct effect on HDL is not known. Here we investigated to determine whether Lp(a) had any effect on the ABCA1 pathway of HDL production in liver cells. Incubation of HepG2 cells with Lp(a) upregulated the PPARγ protein by 1.7-fold and the liver X receptor α protein by 3-fold. This was accompanied by a 1.8-fold increase in ABCA1 protein and a 1.5-fold increase in cholesterol efflux onto apoA1. We showed that Lp(a) was internalized by HepG2 cells, however, the ABCA1 response to Lp(a) was mediated by the selective uptake of oxidized phospholipids (oxPLs) from Lp(a) via the scavenger receptor-B1 and not by Lp(a) internalization per se. We conclude that there is a biological connection between Lp(a) and HDL through the ability of Lp(a)'s oxPLs to upregulate HDL biosynthesis.

摘要

脂蛋白(a)[Lp(a)]水平升高是心血管疾病（CVD）发生的一个公认危险因素。虽然Lp(a)水平被认为独立于其他血浆脂蛋白，但一些试验报告了Lp(a)与高密度脂蛋白（HDL）之间存在正相关。Lp(a)是否对HDL有直接影响尚不清楚。在此，我们进行研究以确定Lp(a)是否对肝细胞中HDL产生的ATP结合盒转运体A1（ABCA1）途径有任何影响。用Lp(a)孵育HepG2细胞使过氧化物酶体增殖物激活受体γ（PPARγ）蛋白上调1.7倍，肝脏X受体α（LXRα）蛋白上调3倍。这伴随着ABCA1蛋白增加1.8倍以及向载脂蛋白A1（apoA1）的胆固醇流出增加1.5倍。我们发现Lp(a)被HepG2细胞内化，然而，ABCA1对Lp(a)的反应是由通过清道夫受体-B1从Lp(a)选择性摄取氧化磷脂（oxPLs）介导的，而非Lp(a)本身的内化。我们得出结论，通过Lp(a)的oxPLs上调HDL生物合成的能力，Lp(a)与HDL之间存在生物学联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/5ff777fbfb4f/1318fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/b6d8405f7afd/1318fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/480b89d4aadc/1318fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/da0b4b1e9509/1318fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/a453b3b8a1e6/1318fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/8222caf9b72a/1318fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/dc3cce85de65/1318fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/5ff777fbfb4f/1318fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/b6d8405f7afd/1318fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/480b89d4aadc/1318fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/da0b4b1e9509/1318fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/a453b3b8a1e6/1318fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/8222caf9b72a/1318fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/dc3cce85de65/1318fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09be/4479336/5ff777fbfb4f/1318fig7.jpg

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