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on February 16, 2006

Arteriosclerosis, Thrombosis, and Vascular Biology. 2006
Published online before print February 16, 2006, doi: 10.1161/01.ATV.0000209998.73303.b5
A more recent version of this article appeared on May 1, 2006
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Submitted on August 25, 2005
Accepted on February 1, 2006

Molecular Dissection of Angiotensin II-Activated Human LOX-1 Promoter

Jiawei Chen ; Yong Liu ; Hongmei Liu ; Paul L. Hermonat ; and Jawahar L. Mehta *

From the Departments of Internal Medicine (J.C., Y.L., H.L., P.L.H., J.L.M.) and Physiology and Biophysics (J.C.), University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Ark.

* To whom correspondence should be addressed. E-mail: MehtaJL{at}uams.edu.

Objective--LOX-1, a receptor for oxidized low-density lipoprotein, plays a critical role in atherosclerosis. Its expression is upregulated by pro-atherogenic stimuli, such as angiotensin II (Ang II). In this study, we explored LOX-1 transcriptional promoter activation in response to Ang II in human coronary artery endothelial cells (HCAECs).

Methods and Results--We constructed full-length and deletion LOX-1 promoter mutants and examined their activation in response to Ang II in HCAECs. The Ang II (1 µmol/L for 24 hours) markedly induced LOX-1 promoter activity beyond the basal level, and a 116-bp fragment (between nt -2247 and -2131) was necessary for this induction. Within this 116-bp promoter fragment, there is a potential binding motif for transcription factor NF-{kappa}B. By EMSA, we observed the activation of NF-{kappa}B by Ang II. The critical role of NF-{kappa}B in Ang II-induced LOX-1 promoter activation was confirmed by mutagenesis assay, and further confirmed by blocking NF-{kappa}B activation with the NF-{kappa}B inhibitor caffeic acid phenethyl ester or NF-{kappa}B p65 siRNA.

Conclusion--This study strongly suggests that Ang II, by activating NF-{kappa}B, induces LOX-1 promoter activation.
Key words: LOX-1 • Ang II • oxLDL • transcription factor • NF-{kappa}B • oxidative stress




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