Endothelin-1 plus oxidized low-density lipoprotein, but neither alone, increase human monocyte adhesion to endothelial cells

2001 ◽  
Vol 101 (6) ◽  
pp. 731 ◽  
Author(s):  
M. R. LANGENFELD ◽  
S. NAKHLA ◽  
A. K. DEATH ◽  
W. JESSUP ◽  
D. S. CELERMAJER
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Human Monocyte ◽  
Low Density ◽  
Monocyte Adhesion ◽  
Oxidized Low Density Lipoprotein ◽  
Endothelin 1

scholarly journals Oxidized low-density lipoprotein stimulates monocyte adhesion to glomerular endothelial cells

1999 ◽  
Vol 55 (6) ◽  
pp. 2192-2202 ◽  
Author(s):  
Vaijinath S. Kamanna ◽  
Rama Pai ◽  
Hunjoo Ha ◽  
Michael A. Kirschenbaum ◽  
Daeyoung D. Roh
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Monocyte Adhesion ◽  
Oxidized Low Density Lipoprotein ◽  
Glomerular Endothelial Cells

Augmented endothelial uptake of oxidized low-density lipoprotein in response to endothelin-1

2002 ◽  
Vol 103 (s2002) ◽  
pp. 9S-12S ◽  
Author(s):  
Henning MORAWIETZ ◽  
Nicole DUERRSCHMIDT ◽  
Bernd NIEMANN ◽  
Jan GALLE ◽  
Tatsuya SAWAMURA ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Receptor Blockade ◽  
Low Density ◽  
Pathophysiological Mechanism ◽  
Endothelin Receptor ◽  
Oxidized Low Density Lipoprotein ◽  
Endothelin 1 ◽  
Atherosclerotic Lesions

Endothelin-1 (ET-1) may be involved in the development and progression of atherosclerosis. Furthermore, endothelin receptor blockade was shown to reduce the formation of atherosclerotic lesions in experimental studies. Another potent pro-atherosclerotic risk factor is oxidized low-density lipoprotein (oxLDL). Endothelial cells mediate the uptake of oxLDL by the recently identified lectin-like oxLDL receptor-1 (LOX-1), which accumulates in atherosclerotic lesions. In the present study, we analysed the effects of ET-1 on oxLDL uptake and LOX-1 expression in primary cultures of human umbilical vein endothelial cells (HUVEC). ET-1 stimulated uptake of oxLDL in HUVEC, which reached a maximum after 1h. In further studies, we found a similar induction of LOX-1 mRNA and protein expression in response to ET-1. The augmented oxLDL uptake and the increased LOX-1 expression in response to ET-1 are mediated by the endothelin receptor B. Our data support a new pathophysiological mechanism by which locally and systemically increased ET-1 levels, e.g. in hypertensive patients, could promote LOX-1-mediated oxLDL uptake in human endothelial cells. This mechanism could promote the development and progression of endothelial dysfunction and atherosclerosis. In addition, endothelin receptor blockade could be considered as a new anti-atherosclerotic therapeutic principle.

Endothelin-1 plus oxidized low-density lipoprotein, but neither alone, increase human monocyte adhesion to endothelial cells

2001 ◽  
Vol 101 (6) ◽  
pp. 731-738 ◽  
Author(s):  
M.R. LANGENFELD ◽  
S. NAKHLA ◽  
A.K. DEATH ◽  
W. JESSUP ◽  
D.S. CELERMAJER
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Human Monocytes ◽  
Oxidized Low Density Lipoprotein ◽  
Endothelin 1

Endothelin-1 is a potent vasoconstrictor and mitogenic peptide that is implicated in the atherosclerosis of apolipoprotein E-deficient mice and may promote atherogenesis in humans. We hypothesized that endothelin-1 might promote the adhesion of monocytes to endothelial cells, a key early event in atherosclerosis. We investigated the adhesion of primary human monocytes (isolated by elutriation) to human umbilical vein endothelial cell cultures after incubation with endothelin-1 (0.1 and 0.01nM; approximately physiological concentrations), copper-oxidized low-density lipoprotein (LDL) (0.1mg/ml) and a combination of the two. After a 4h incubation with 0.1 or 0.01nM endothelin-1 combined with oxidized LDL, adhesion was increased to 120±4% (P < 0.001 compared with control) and 118±4% (P < 0.002) respectively, whereas neither substance alone increased adhesion (92-104% of control values; not significant). Neither endothelin receptor A blockade nor co-incubation with anti-fibronectin antibody inhibited the pro-adhesive effects of endothelin-1 plus oxidized LDL (115±7% and 115±3% of control compared with 120±4% respectively; not significant). Endothelial cell expression of intercellular adhesion molecule-1, vascular adhesion molecule-1 and E-selectin were unchanged throughout the experiment. Therefore physiological concentrations of endothelin-1 and oxidized LDL may act synergistically to increase the adhesion of human monocytes to endothelial cells, contributing in part to the observed pro-atherogenic effects of endothelin-1.

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