Molecular Dissection of Angiotensin Ii-activated Human Lox-1 Promoter.
From: Department of Internal Medicine, University of Arkansas for Medical Sciences, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.
Arteriosclerosis, thrombosis, and vascular biology
- Publish Date: May 2006
- ISSN: 1524-4636
- Volume: 26
- Issue: 5
- Pages: 1163-8
- Medium: Internet
- Language: English
- Citation (JAMA): Chen Jiawei, Liu Yong, Liu Hongmei, et al. Molecular Dissection of Angiotensin Ii-activated Human Lox-1 Promoter.. Arterioscler. Thromb. Vasc. Biol. May 2006;26:1163-8
Abstract
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 micromol/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-kappaB. By EMSA, we observed the activation of NF-kappaB by Ang II. The critical role of NF-kappaB in Ang II-induced LOX-1 promoter activation was confirmed by mutagenesis assay, and further confirmed by blocking NF-kappaB activation with the NF-kappaB inhibitor caffeic acid phenethyl ester or NF-kappaB p65 siRNA. CONCLUSIONS: This study strongly suggests that Ang II, by activating NF-kappaB, induces LOX-1 promoter activation.
Mesh Headings (Keywords): Angiotensin II, Binding Sites, Cells, Cultured, Electrophoretic Mobility Shift Assay, Endothelial Cells, Humans, NF-kappa B, Promoter Regions (Genetics), Scavenger Receptors, Class E
Check for Full Text / PubMed Unique Identifier (PMID): 16484599
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