This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 26/5/1163    most recent 01.ATV.0000209998.73303.b5v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, J. Articles by Mehta, J. L. Search for Related Content PubMed PubMed Citation Articles by Chen, J. Articles by Mehta, J. L.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1163.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Jiawei Chen; Yong Liu; Hongmei Liu; Paul L. Hermonat; 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.

Correspondence to J.L. Mehta, MD, PhD, Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences, 4301 W Markham St, Slot 532, Little Rock, AR 72205-7199. 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-B. By EMSA, we observed the activation of NF-B by Ang II. The critical role of NF-B in Ang II–induced LOX-1 promoter activation was confirmed by mutagenesis assay, and further confirmed by blocking NF-B activation with the NF-B inhibitor caffeic acid phenethyl ester or NF-B p65 siRNA.

Conclusion— This study strongly suggests that Ang II, by activating NF-B, induces LOX-1 promoter activation.

In this study, we explored LOX-1 transcriptional promoter activation in response to angiotensin II (Ang II) in human coronary artery endothelial cells. This study strongly suggests that Ang II, by activating NF-B, induces LOX-1 promoter activation.

Key Words: LOX-1 • Ang II • oxLDL • transcription factor • NF-B • oxidative stress

This article has been cited by other articles:

				C. Hu, A. Dandapat, L. Sun, M. R. Marwali, N. Inoue, F. Sugawara, K. Inoue, Y. Kawase, K.-i. Jishage, H. Suzuki, et al. Modulation of Angiotensin II-Mediated Hypertension and Cardiac Remodeling by Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Deletion Hypertension, September 1, 2008; 52(3): 556 - 562. [Abstract] [Full Text] [PDF]

				E. D. Frohlich Excitement of Clinical Investigation: New Basic Mechanisms of Action After Drug Introduction Hypertension, September 1, 2008; 52(3): 465 - 466. [Full Text] [PDF]

				A. Bukowska, L. Schild, G. Keilhoff, D. Hirte, M. Neumann, A. Gardemann, K. H. Neumann, F.-W. Rohl, C. Huth, A. Goette, et al. Mitochondrial Dysfunction and Redox Signaling in Atrial Tachyarrhythmia Experimental Biology and Medicine, May 1, 2008; 233(5): 558 - 574. [Abstract] [Full Text] [PDF]

				C. Hu, A. Dandapat, and J. L Mehta Angiotensin II Induces Capillary Formation From Endothelial Cells Via the LOX-1 Dependent Redox-Sensitive Pathway Hypertension, November 1, 2007; 50(5): 952 - 957. [Abstract] [Full Text] [PDF]