Peroxisome Proliferator–activated Receptor Activators Inhibit Oxidized Low-density Lipoprotein–induced Endothelin-1 Secretion in Endothelial Cells

2002 ◽  
Vol 40 (6) ◽  
pp. 822-831 ◽  
Author(s):  
F. Martin-Nizard ◽  
C. Furman ◽  
P. Delerive ◽  
A. Kandoussi ◽  
J. C. Fruchart ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Peroxisome Proliferator Activated Receptor ◽  
Endothelin 1

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.

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