scholarly journals Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transcriptional regulation by Oct-1 in human endothelial cells: implications for atherosclerosis

2005 ◽  
Vol 393 (1) ◽  
pp. 255-265 ◽  
Author(s):  
Jiawei Chen ◽  
Yong Liu ◽  
Hongmei Liu ◽  
Paul L. Hermonat ◽  
Jawahar L. Mehta
Keyword(s):  
Endothelial Cells ◽  
Core Promoter ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Binding Motif ◽  
Low Density ◽  
Ang Ii ◽  
Oxidized Low Density Lipoprotein ◽  
Promoter Activation

LOX-1, a receptor for ox-LDL (oxidized low-density lipoprotein), has recently been determined to play a critical role in the progression of atherosclerosis. LOX-1 expression (mRNA and protein) has been shown to be up-regulated by pro-atherogenic stimuli, such as ox-LDL and Ang II (angiotensin II). However, the molecular mechanisms of these up-regulations are unclear. In the present study, we explored LOX-1 transcriptional promoter activation in response to ox-LDL and Ang II. Under basal states, LOX-1 core promoter (LOX-1 −35/+36) was found to be sufficient for its basal activity in HCAECs (human coronary artery endothelial cells). More importantly, we found that ox-LDL (60 μg/ml for 24 h) induced LOX-1 promoter activity significantly and that a 105 bp fragment (between nt −1599 and −1494) was required for this activation. Within this 106 bp fragment, there is a potential binding motif for the transcription factor Oct-1 (octamer-1). By electrophoretic mobility-shift assay, we observed the activation of Oct-1 by ox-LDL. The critical role of Oct-1 in ox-LDL-induced LOX-1 promoter activation was further confirmed by mutagenesis assay. For comparison, we also examined LOX-1 promoter activation in response to Ang II (1 μmol/l for 24 h). Interestingly, another promoter region, between nt −2336 and −1990, was required for Ang II-induced LOX-1 promoter activation. In conclusion, the present study strongly suggests that ox-LDL, by activating Oct-1, induces LOX-1 promoter activation. Furthermore, this study suggests that while ox-LDL and Ang II both induce LOX-1 expression in HCAECs, the underlying mechanisms of promoter activation are different from each other.

scholarly journals The Osteoclast-Associated Receptor (OSCAR) Is a Novel Receptor Regulated by Oxidized Low-Density Lipoprotein in Human Endothelial Cells

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4915-4926 ◽  
Author(s):  
Claudia Goettsch ◽  
Martina Rauner ◽  
Kathrin Sinningen ◽  
Susann Helas ◽  
Nadia Al-Fakhri ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Osteoclast Differentiation ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Human Endothelial Cells ◽  
Apolipoprotein E Knockout Mice

Cross talks between the vascular and immune system play a critical role in vascular diseases, in particular in atherosclerosis. The osteoclast-associated receptor (OSCAR) is a regulator of osteoclast differentiation and dendritic cell maturation. Whether OSCAR plays a role in vascular biology and has an impact on atherogenic processes provoked by proinflammatory stimuli is yet unknown. We identified OSCAR on the surface of human primary endothelial cells. Stimulation of endothelial cells with oxidized low-density lipoprotein (oxLDL) caused a time- and dose-dependent induction of OSCAR, which was lectin-like oxidized LDL receptor 1 and Ca2+ dependent. OSCAR was transcriptionally regulated by oxLDL as shown by OSCAR promoter analysis. Specific inhibition of the nuclear factor of activated T cells (NFAT) pathway prevented the oxLDL-mediated increase of endothelial OSCAR expression. As assessed by EMSA, oxLDL induced binding of NFATc1 to the OSCAR promoter. Notably, in vivo-modified LDL from patients with diabetes mellitus stimulated OSCAR mRNA expression in human endothelial cells. Furthermore, apolipoprotein E knockout mice fed a high-fat diet showed an enhanced aortic OSCAR expression associated with increased expression of NFATc1. In summary, OSCAR is expressed in vascular endothelial cells and is regulated by oxLDL involving NFATc1. Our data suggest that OSCAR, originally described in bone as immunological mediator and regulator of osteoclast differentiation, may be involved in cell activation and inflammation during atherosclerosis.

MicroRNA‐328 ameliorates oxidized low‐density lipoprotein‐induced endothelial cells injury through targeting HMGB1 in atherosclerosis

2018 ◽  
Vol 120 (2) ◽  
pp. 1643-1650 ◽  
Author(s):  
Chun‐Yang Wu ◽  
Zhao‐Feng Zhou ◽  
Bin Wang ◽  
Zun‐Ping Ke ◽  
Zhong‐Chun Ge ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein

LOX-1-dependent transcriptional regulation in response to oxidized LDL treatment of human aortic endothelial cells

2009 ◽  
Vol 296 (6) ◽  
pp. C1329-C1337 ◽  
Author(s):  
Mark D. Mattaliano ◽  
Christine Huard ◽  
Wei Cao ◽  
Andrew A. Hill ◽  
Wenyan Zhong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Human Aortic Endothelial Cell ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Camp Response Element ◽  
Response Element ◽  
Aortic Endothelial

Oxidized low-density lipoprotein (OxLDL) has been implicated as a proatherogenic factor with a pathological role in the induction of endothelial dysfunction. Endothelial cells bind and uptake OxLDL primarily through the scavenger receptor lectin-like oxidized-low-density lipoprotein receptor-1 (LOX-1), which is believed to mediate critical effects of OxLDL in endothelial cells. To examine the biological events following LOX-1 activation by OxLDL, we used cDNA microarray analysis to globally analyze gene expression changes induced by OxLDL treatment of human aortic endothelial cell line (HAECT) cells overexpressing LOX-1. Consistent with reported functions of OxLDL, in control HAECT cells, OxLDL elicited gene changes in the oxidative stress pathway and other signaling pathways related to OxLDL. With OxLDL treatment, LOX-1-dependent gene expression changes associated with inflammation, cell adhesion, and signal transduction were observed. The transcripts of a number of cytokines and chemokines were induced, which included interleukin-8, CXCL2, CXCL3, and colony-stimulating factor-3. The secretion of these cytokines was confirmed by enzyme-linked immunosorbent assay analysis. In addition, our data revealed a novel link between LOX-1 and a number of genes, including Delta/notch-like epidermal growth factor repeat containing, stanniocalcin-1, cAMP response element modulator, and dual specificity phosphatase 1. Promoter analysis on the genes that changed as a result of LOX-1 activation by OxLDL allowed us to identify early growth response 1 and cAMP response element-binding protein as potential novel transcription factors that function downstream of LOX-1. Our study has enabled us to elucidate the gene expression changes following OxLDL activation of LOX-1 in endothelial cells and discover novel downstream targets for LOX-1.

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