Abstract:
RATIONALE:Lipoprotein(a) [Lp(a)] is a low-density lipoprotein-like lipoprotein and important cardiovascular risk factor whose cognate receptor and intracellular fate remains unknown. OBJECTIVE:Our study aimed to determine the intracellular trafficking pathway for Lp(a) and the receptor responsible for its uptake in liver cells. METHODS AND RESULTS:Human hepatoma cells were treated with Lp(a) purified from human plasma and Lp(a) uptake studied using Western blot analysis and intracellular localization of Lp(a) by confocal microscopy. Lp(a) was maximally internalized by 2 hours and was detected by an antiapo(a) antibody to be localized to Rab5-positive early endosomes, the trans-Golgi network, and subsequently Rab11-positive recycling endosomes. In human hepatoma cells, the apo(a) component from the internalized Lp(a) was resecreted back into the cellular media, whereas the low-density lipoprotein component was localized to the lysosomal compartment. Lp(a) internalization was reduced 0.35-fold in HAP1 and 0.33-fold in human hepatoma cells in which the plasminogen receptor (KT) was knocked out. Conversely, Lp(a) internalization was enhanced 2-fold in HAP1 and 1.6-fold in human hepatoma cells in which plasminogen receptor (KT) was overexpressed, showing for the first time the role of a specific plasminogen receptor in Lp(a) uptake. CONCLUSIONS:The novel findings that Lp(a) is internalized by the plasminogen receptor, plasminogen receptor (KT), and the apo(a) component is recycled may have important implications for the catabolism and function of Lp(a).
journal_name
Circ Resjournal_title
Circulation researchauthors
Sharma M,Redpath GM,Williams MJ,McCormick SPdoi
10.1161/CIRCRESAHA.116.310272subject
Has Abstractpub_date
2017-03-31 00:00:00pages
1091-1102issue
7eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.310272journal_volume
120pub_type
杂志文章abstract::Peripheral blood (PB)-derived CD14+ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34-/CD14+ cells are involved in reendothelialization after carotid balloon injury. Although neither hem...
journal_title:Circulation research
pub_type: 杂志文章
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journal_title:Circulation research
pub_type: 杂志文章
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journal_title:Circulation research
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journal_title:Circulation research
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2004-03-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2008-10-10 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2016-08-19 00:00:00
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journal_title:Circulation research
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更新日期:2006-08-04 00:00:00
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更新日期:2011-08-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.182535
更新日期:2009-01-30 00:00:00
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journal_title:Circulation research
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journal_title:Circulation research
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更新日期:1991-12-01 00:00:00
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更新日期:2003-03-21 00:00:00
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pub_type: 杂志文章,评审
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更新日期:1987-06-01 00:00:00
abstract::Congenital heart defects affect almost 1% of human newborns. Recently, mutations in Notch ligands and receptors have been found to cause a variety of heart defects in rodents and humans. However, the molecular effects downstream of Notch are still poorly understood. Here we report that combined inactivation of Hey1 an...
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更新日期:2007-03-30 00:00:00
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更新日期:2017-03-17 00:00:00
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更新日期:2005-12-09 00:00:00
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更新日期:1985-08-01 00:00:00