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.
|Tipologia:||Articolo su rivista|
|Citazione:||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.|
|Settore Scientifico Disciplinare:||Settore MED/11 - Malattie dell'Apparato Cardiovascolare|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1006/bbrc.2001.6070|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2001|
|Titolo:||Inhibition of LOX-1 by statins may relate to upregulation of eNOS|
|Autori:||Mehta, JL; Li, DY; Chen, HJ; Joseph, J; Romeo, F|
|Appare nelle tipologie:||01 - Articolo su rivista|