Redox-sensitive regulation of LOX-1 gene expression in vascular endothelium

Oxidative stress has been implicated in atherosclerosis and its underlying conditions. LOX-1 is a novel endothelial receptor for oxidized low-density lipoprotein which might mediate endothelial dysfunction and subsequent athe rogenesis. In the present study, we examined LOX-1 gene regulation by oxida tive stress. First, superoxide anions generated by hypoxanthine and xanthin e oxidase as well as hydrogen peroxide increased LOX-1 mRNA expression in c ultured aortic endothelial cells. Homocysteine, an atherogenic substance be lieved to exert its effects through oxidative stress, enhanced endothelial LOX-1 gene expression, which was suppressed by N-acetylcysteine. Second, ra ts receiving angiotensin II for 10 days manifested hypertension and LOX-1 u pregulation in aortic endothelium via AT1 receptor. Tempo, a superoxide dis mutase mimetic, alleviated LOX-1 augmentation induced by angiotensin II. Th ese results indicated redox-sensitive upregulation of LOX-1 mRNA in both in vitro and in vivo systems, suggesting its potential role in atherosclerosi s. (C) 2001 Academic Press.