LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis; both of these conditions are associated with diminished expression of constitutive endothelial nitric oxide synthase (eNOS). Recent studies show that HMG CoA reductase inhibitors (statins) exert cardioprotective effect. We examined the role of LOX-1 in eNOS expression and modulation of this relationship by two different statins, simvastatin and atorvastatin in human coronary artery endothelial cells (HCAECs). OxLDL (40 mug/ml) upregulated the expression of LOX-1; simultaneously, there was a reduction in eNOS expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 muM) reduced ox-LDL-induced upregulation of LOX-1 and downregulation of eNOS (both P < 0.05). High concentration of statins (10 μM) was more potent than the low concentration (1 μM) (P < 0.05). Both statins also attenuated ox-LDL-mediated activation of MAP kinase. These observations indicate that statins attenuate the effect of ox-LDL on eNOS expression. Inhibitory effect on LOX-1 and subsequently MAP kinase activity provides a potential mechanism of beneficial effects of statins beyond lowering cholesterol. (C) 2001 Elsevier Science.

Mehta, J.L., Li, D.Y., Chen, H.J., Joseph, J., & Romeo, F. (2001). Inhibition of LOX-1 by statins may relate to upregulation of eNOS. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 289(4), 857-861 [10.1006/bbrc.2001.6070].

Inhibition of LOX-1 by statins may relate to upregulation of eNOS

ROMEO, FRANCESCO
2001

Abstract

LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis; both of these conditions are associated with diminished expression of constitutive endothelial nitric oxide synthase (eNOS). Recent studies show that HMG CoA reductase inhibitors (statins) exert cardioprotective effect. We examined the role of LOX-1 in eNOS expression and modulation of this relationship by two different statins, simvastatin and atorvastatin in human coronary artery endothelial cells (HCAECs). OxLDL (40 mug/ml) upregulated the expression of LOX-1; simultaneously, there was a reduction in eNOS expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 muM) reduced ox-LDL-induced upregulation of LOX-1 and downregulation of eNOS (both P < 0.05). High concentration of statins (10 μM) was more potent than the low concentration (1 μM) (P < 0.05). Both statins also attenuated ox-LDL-mediated activation of MAP kinase. These observations indicate that statins attenuate the effect of ox-LDL on eNOS expression. Inhibitory effect on LOX-1 and subsequently MAP kinase activity provides a potential mechanism of beneficial effects of statins beyond lowering cholesterol. (C) 2001 Elsevier Science.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/11 - Malattie dell'Apparato Cardiovascolare
English
adhesion molecules; endothelial cells; LOX-1; oxidized-low density lipoprotein
LOW-DENSITY-LIPOPROTEIN; ARTERY ENDOTHELIAL-CELLS; OXIDIZED LDL RECEPTOR-1; NITRIC-OXIDE SYNTHASE; UP-REGULATION; ATHEROSCLEROTIC LESIONS; EXPRESSION; ADHESION; ANTISENSE
Mehta, J.L., Li, D.Y., Chen, H.J., Joseph, J., & Romeo, F. (2001). Inhibition of LOX-1 by statins may relate to upregulation of eNOS. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 289(4), 857-861 [10.1006/bbrc.2001.6070].
Mehta, J; Li, D; Chen, H; Joseph, J; Romeo, F
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/57774
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