LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis. LOX-1 activation also plays an important role in monocyte adhesion to endothelial cells. A number of studies show that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduce total LDL cholesterol and exert a cardioprotective effect. We examined the modulation of LOX-1 expression and its function by two different statins, simvastatin and atorvastatin, in human coronary artery endothelial cells (HCAECs). We observed that ox-LDL (40 mug/ml) treatment upregulated the expression of E- and P-selectins, VCAM-1 and ICAM-1 in HCAECs. Ox-LDL mediated these effects via LOX-1, since antisense to LOX-1 mRNA decreased LOX-1 expression and subsequent adhesion molecule expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 muM) reduced ox-LDL-induced expression of LOX-1 as well as adhesion molecules (all P < 0.05). A high concentration of statins (10 μM) was more potent than the low concentration (1 μM) (P < 0.05). Both statins reduced ox-LDL-mediated activation of the redox-sensitive nuclear factor-kappaB (NF-kappaB) but not AP-1. These observations indicate that LOX-1 activation plays an important role in ox-LDL-induced expression of adhesion molecules. Inhibition of expression of LOX-1 and adhesion molecules and activation of NF-kappaB may be another mechanism of beneficial effects of statins in vascular diseases.

Li, D.Y., Chen, H.J., Romeo, F., Sawamura, T., Saldeen, T., & Mehta, J.L. (2002). Statins modulate oxidized low-density lipoprotein-mediated adhesion molecule expression in human coronary artery endothelial cells: role of LOX-1. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 302(2), 601-605 [10.1124/jpet.102.034959].

Statins modulate oxidized low-density lipoprotein-mediated adhesion molecule expression in human coronary artery endothelial cells: role of LOX-1

ROMEO, FRANCESCO;
2002

Abstract

LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis. LOX-1 activation also plays an important role in monocyte adhesion to endothelial cells. A number of studies show that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduce total LDL cholesterol and exert a cardioprotective effect. We examined the modulation of LOX-1 expression and its function by two different statins, simvastatin and atorvastatin, in human coronary artery endothelial cells (HCAECs). We observed that ox-LDL (40 mug/ml) treatment upregulated the expression of E- and P-selectins, VCAM-1 and ICAM-1 in HCAECs. Ox-LDL mediated these effects via LOX-1, since antisense to LOX-1 mRNA decreased LOX-1 expression and subsequent adhesion molecule expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 muM) reduced ox-LDL-induced expression of LOX-1 as well as adhesion molecules (all P < 0.05). A high concentration of statins (10 μM) was more potent than the low concentration (1 μM) (P < 0.05). Both statins reduced ox-LDL-mediated activation of the redox-sensitive nuclear factor-kappaB (NF-kappaB) but not AP-1. These observations indicate that LOX-1 activation plays an important role in ox-LDL-induced expression of adhesion molecules. Inhibition of expression of LOX-1 and adhesion molecules and activation of NF-kappaB may be another mechanism of beneficial effects of statins in vascular diseases.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/11 - Malattie dell'Apparato Cardiovascolare
English
NITRIC-OXIDE SYNTHASE; RECEPTOR MESSENGER-RNA; SMOOTH-MUSCLE CELLS; SCAVENGER RECEPTOR; UP-REGULATION; ATHEROSCLEROTIC LESIONS; REDUCTASE INHIBITORS; LDL RECEPTOR-1; ACTIVATION; SIMVASTATIN
5
Li, D.Y., Chen, H.J., Romeo, F., Sawamura, T., Saldeen, T., & Mehta, J.L. (2002). Statins modulate oxidized low-density lipoprotein-mediated adhesion molecule expression in human coronary artery endothelial cells: role of LOX-1. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 302(2), 601-605 [10.1124/jpet.102.034959].
Li, D; Chen, H; Romeo, F; Sawamura, T; Saldeen, T; Mehta, J
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/57772
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