Stimulation of phagocyte adhesion to endothelial cells by modified VLDL and HDL requires scavenger receptor BI.
Mol Cell Biochem
; 383(1-2): 21-8, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23852455
ABSTRACT
Hyperglycemia- and oxidative stress-induced modification of circulating lipoproteins is being increasingly recognized as an important pathogenetic factor for diabetic cardiovascular damages. This study was designed to investigate the impact of modified very low-density lipoprotein and high-density lipoprotein on phagocyte adhesion to endothelial cells and the involvement of scavenger receptor class B type 1 (SR-BI) in this process. Native lipoproteins were isolated by density gradient ultracentrifugation and in vitro glycoxidative or oxidative modification was performed in the presence of glucose or sodium hypochlorite, respectively. One hour co-incubation experiments with lipoproteins, freshly prepared polymorphonuclear leukocytes (PMN), and venous endothelial cells (HUVEC) were performed in the presence or absence of different scavenger receptors and signal transduction inhibitors. PMN adhesion to HUVEC was quantified fluorimetrically. We demonstrated that oxidized and glycoxidized lipoproteins promote adhesion of PMN to HUVEC from 1.5- to 2.5-fold with oxidized lipoproteins having the greatest effect. Treatment with the highly specific SR-BI inhibitor, BLT-1 produced substantial reduction of lipoprotein-induced adhesion to endothelial cells. Native and modified lipoproteins recruited extracellular signal-regulated kinase (ERK 1/2), p38 mitogen-activated protein kinase, and Janus kinase 2 as downstream signaling pathways for adhesion. From this study, it could be concluded that modification of lipoproteins plays a crucial role in atherosclerotic progression and SR-BI may be considered as a potential therapeutic target for the prevention of diabetic cardiovascular complications.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fagócitos
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Receptores Depuradores Classe B
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Células Endoteliais da Veia Umbilical Humana
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Lipoproteínas HDL
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Lipoproteínas VLDL
Limite:
Humans
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2013
Tipo de documento:
Article