LOX-1 Transcription

The importance of the lectin-like oxidized LDL receptor (LOX-1) gene in cardiovascular and other diseases is slowly being revealed. LOX-1 gene expression appears to be a “canary in a coal mine” for atherogenesis, being strongly up-regulated early on in a number of cell types when they are activated,...

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Bibliographic Details
Published in:Cardiovascular drugs and therapy 2011-10, Vol.25 (5), p.393-400
Main Authors: Hermonat, Paul L., Zhu, Hongqing, Cao, Maohua, Mehta, Jawahar L.
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis - genetics
Atherosclerosis - metabolism
Cardiology
Gene Expression Regulation
Humans
Medicine
Medicine & Public Health
Review Article
Scavenger Receptors, Class E - biosynthesis
Scavenger Receptors, Class E - genetics
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription, Genetic
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Summary:The importance of the lectin-like oxidized LDL receptor (LOX-1) gene in cardiovascular and other diseases is slowly being revealed. LOX-1 gene expression appears to be a “canary in a coal mine” for atherogenesis, being strongly up-regulated early on in a number of cell types when they are activated, and predicting the sites of future disease. From this early time point the LOX-1 protein often participates in the disease process itself. While gene/protein expression can be regulated on a multiplicity of levels, the most basic and important mode of regulation is usually transcriptional. There are very few studies on the transcriptional regulation of the human LOX-1 promoter; fewer still on definitive mapping of the transcription factors involved. It is known that a wide variety of stimuli up-regulate LOX-1, usually/probably on the transcriptional level. Angiotensin II (Ang II) is one important regulator of renin-angiotensin system and stimulator LOX-1. Ang II is known to up-regulate LOX-1 transcription through an NF-kB motif located at nt −2158. Oxidized low density lipoprotein (ox-LDL) is another important cardiovascular regulator, particularly of atherosclerotic disease, and a strong stimulator of LOX-1. Ox-LDL is known to up-regulate LOX-1 transcription through an Oct-1 motif located at nt −1556. The subsequent enhanced LOX-1 receptor numbers and their binding by ox-LDL ligand triggers a positive feedback loop, increasing further LOX-1 expression, with a presently unknown regulatory governor. The Oct-1 gene also has its own Oct-1-driven positive feedback loop, which likely also contributes to LOX-1 up-regulation. There is also data which suggests the involvement of the transcription factor AP-1 during stimulation with Phorbol 12-myristate acetate. While the importance of NF-κB as a transcriptional regulator of cardiovascular-relevant genes is well known, the importance of Oct-1 is not. Data suggests that Oct-1-mediated up-regulation of transcription is an early event in the stimulation of LOX-1 by ox-LDL. Yet Oct-1 also down-regulates cardiovascular-relevant genes by suppressing NF-κB transactivation. Thus, Oct-1 is presently somewhat of an enigma, up-regulating and down-regulating genes seemingly at random without an overall theme (with the exception of cell cycle). Yet the up-regulation of LOX-1 by ox-LDL is a very important event in atherogenesis (both early and late) and Oct-1 is, therefore, an important transcriptional gatekeeper of this important at
ISSN:0920-3206
1573-7241
DOI:10.1007/s10557-011-6322-8