title: Lipoprotein (a) upregulates ABCA1 in liver cells via scavenger receptor-B1 through its oxidized phospholipids.
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.
authors: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors: Monika
authors: M
authors: Sharma
authors: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors: Anne
authors: A
authors: Von Zychlinski-Kleffmann
authors: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors: Carolyn M
authors: CM
authors: Porteous
authors: Departments of Surgical Sciences University of Otago, Dunedin, New Zealand.
authors: Gregory T
authors: GT
authors: Jones
authors: Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors: Michael J A
authors: MJ
authors: Williams
authors: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors: Sally P A
authors: SP
authors: McCormick
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D018955:CD36 Antigens / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D017270:Lipoprotein(a) / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018955:CD36 Antigens; D017270:Lipoprotein(a); D010743:Phospholipids
keywords: adenosine 5′-triphosphate binding cassette transporter A1; cholesterol efflux; high density lipoprotein; nuclear receptor/liver X receptor; nuclear receptor/peroxisome proliferator-activated receptor