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

Chen, Jiawei; Liu, Yong; Li, Hongmei; Hermonat, Paul L.; Mehta, Jawahar L.

doi:10.1042/bj20050845

Cited by 45 publications

(41 citation statements)

References 35 publications

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“…In this study, we did not observe the complete blockade of NF-B activity by the siRNA; we postulate that it is caused by the relatively low transfection efficiency of endothelial cells, as we observed previously. 13 This explanation is supported by the observation that NF-B p65 subunit is still expressed in p65 NF-B siRNA plasmid-transfected cells, though the expression is marked lower than that in cells without transfection. Accordingly, because not all cells are transfected with siRNA plasmid, it is not surprising that p65 NF-B siRNA cannot completely block Ang II-mediated NF-B activation or LOX-1 promoter activation in HCAECs.…”

Section: The Critical Role Of Nf-b In Ang Ii-induced Lox-1 Promoter Asupporting

confidence: 72%

“…In a recent study, we found that a distinct promoter region, between nt Ϫ1595 and Ϫ1494, is required for LOX-1 promoter activation in response to oxLDL. 13 There could be 2 explanations for this observation. First, Ang II and oxLDL both induce intracellular oxidative stress, which then activates the same transcription factor.…”

Section: Analysis Of Ang Ii-induced Lox-1 Promoter Activationmentioning

confidence: 99%

“…13 The 116-bp LOX-1 promoter fragment (between nt Ϫ2247 and Ϫ2131), required for Ang II-induced LOX-1 promoter activation, was obtained by PCR. Complementary oligonucleotides containing putative NF-B binding site (5Ј-AGT TGA GGG GAC TTT CCC AGG C-3Ј), NF-1 binding site (5Ј-TTT TGG ATT GAA GCC AAT ATG ATA A-3Ј), Sp-1 binding site (5Ј-ATT CGA TCG GGG CGG GGC GAG C-3Ј) or AP-2 binding site (5Ј-GAT CGA ACT GAC CGC CCG CGG CCC GT-3Ј) were obtained from Invitrogen.…”

Section: Electrophoretic Mobility Shift Assay (Emsa) Supershift Andmentioning

confidence: 99%

“…13 To delineate whether Ang II activates LOX-1 promoter through this (Oct-1) or another pathway, we analyzed Ang II-mediated activation of human LOX-1 promoter in HCAECs.…”

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

Chen

Liu

et al. 2006

ATVB

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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 mol/L for 24 hours) markedly induced LOX-1 promoter activity beyond the basal level, and a 116-bp fragment (between nt Ϫ2247 and Ϫ2131) was necessary for this induction. Key Words: LOX-1 Ⅲ Ang II Ⅲ oxLDL Ⅲ transcription factor Ⅲ NF-B Ⅲ oxidative stress A therosclerosis and associated diseases are major causes of death in the Western world. High plasma level of low-density lipoprotein (LDL), especially in the form of oxidized LDL (oxLDL), is a major risk factor for atherogenesis. 1 oxLDL plays a critical role in endothelial dysfunction, which appears at the early stages of atherogenesis. 2 In vitro studies have demonstrated that during oxLDL-induced endothelial dysfunction, vascular endothelial cells internalize ox-LDL through a receptor-mediated pathway. Although several scavenger receptors are involved in the internalization of oxLDL in macrophages, these receptors are absent or present only in a very small amount on endothelial cells. 3 Recently, an endothelial oxLDL receptor, LOX-1, was identified on cultured bovine aortic endothelial cells 4 and human coronary artery endothelial cells (HCAECs). 5 Many of the proatherogenic effects of oxLDL in endothelial cells appear to be mediated through LOX-1. 6 In vitro and in vivo studies have shown that LOX-1 expression is upregulated by oxLDL. 7,8 Angiotensin II (Ang II), which participates in atherogenesis, 9 also upregulates the expression of LOX-1. 10 Singh and Mehta 11 recently proposed an interaction between hyperlipidemia and renin-angiotensin system (RAS) activation in the development of atherosclerosis, during which LOX-1 plays a critical role.The nucleotide sequence of human LOX-1 promoter has been identified. 12 Although only a few details are known about the transcription factors that modulate LOX-1 gene expression, a number of potential cis-regulatory elements, such as nuclear factor-B (NF-B) and activator protein-1 (AP-1) binding motif, are found within the LOX-1 promoter sequence. 12 Nonetheless, human LOX-1 transcriptional promoter has not been thoroughly examined on the molecular level.In a recent study, we examined LOX-1 promoter activation in response to oxLDL in HCAECs, and found the transcription factor octamer-1(Oct-1) is essential for this process. 13 To delineate whether Ang II activates LOX-1 promoter through this (Oct-1) or another pathway, we analyzed Ang II-mediated activation of human LOX-1 promoter in HCAECs. Methods and Materials LOX-1 Promoter-Luciferase Reporter Plasmid ConstructionThe promoterless luciferase reporter vector (pGL3 Basic) was o...

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Section: The Critical Role Of Nf-b In Ang Ii-induced Lox-1 Promoter Asupporting

confidence: 72%

Section: Analysis Of Ang Ii-induced Lox-1 Promoter Activationmentioning

confidence: 99%

Section: Electrophoretic Mobility Shift Assay (Emsa) Supershift Andmentioning

confidence: 99%

“…13 To delineate whether Ang II activates LOX-1 promoter through this (Oct-1) or another pathway, we analyzed Ang II-mediated activation of human LOX-1 promoter in HCAECs.…”

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

Chen

Liu

et al. 2006

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“…It has also been demonstrated that ECs apoptosis induced atherosclerotic lesion development and plaque shedding [3][4][5]. Oxidized Low-Density Lipoprotein (ox-LDL), an important atherosclerotic risk factor, may induce ECs apoptosis during the pathogenesis of AS [6][7][8]. Hence, inhibition of ox-LDL induced ECs apoptosis may suggest new therapies in the AS treatment.…”

Section: Introductionmentioning

confidence: 99%

Qiliqiangxin improves oxidized low-density lipoprotein-induced human coronary artery endothelial cells injury

Du¹,

Lv²,

Meng³

et al. 2018

biomedicalresearch

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Qiliqiangxin (QL) has protective effect for the cardiovascular diseases treatment. This study aim to evaluate the effect of QL on the cell viability, cell apoptosis and caspase-3 activity in oxidized LDL (oxLDL)-induced Human Coronary Artery Endothelial Cells (HCAECs). HCAECs were treated with QL (0-1µg/ml) and oxLDL (150 μg/ml). The HCAECs viability was detected by cell proliferation assay and Lactate Dehydrogenase (LDH) release assay. The HCAECs apoptosis was evaluated by the annexin V-FITC assay. The activity of caspase-3 of HCAECs was measured by colorimetric caspase-3 assay. Cell migration assay and capillary-like tube formation assay on Matrigel were performed. Treatment of HCAECs to ox-LDL (150 μg/ml) decreased cell viability, stimulated apoptosis and enhanced caspase-3 activity. In addition, treatment with QL (0.5 µg/ml) alone did not affect cell viability and LDH release. Furthermore, the treatment with QL (0.5 µg/ml) significantly increased ox-LDL (150 μg/ml) decreased cell viability. Treatment with QL (0.5 µg/ml) reduced ox-LDL-stimulated apoptosis and caspase-3 activity in HCAECs in a dose-dependent manner. QL (0.5 µg/ml) attenuated ox-LDL (150 μg/ml) abolished cell migration and tube formation. Our study demonstrated that QL prevents ox-LDLinduced HCAECs injury by decreasing the apoptosis via caspase-3 activity.

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The oxidized‐LDL/LOX‐1 axis in tumor endothelial cells enhances metastasis by recruiting neutrophils and cancer cells

Tsumita

Maishi

Annan

et al. 2022

Intl Journal of Cancer

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Epidemiological relationships between cancer and cardiovascular diseases have been reported, but a molecular basis remains unclear. Some proteoglycans that strongly bind low‐density‐lipoprotein (LDL) are abundant both in atherosclerotic regions and in high metastatic‐tumor tissue. LDL retention is crucial for the initiation of atherosclerosis, although its contribution to malignancy of cancer is not known. In our study, we show the importance of the accumulation of LDL in tumor metastasis. We demonstrated that high metastatic‐tumor tissue contains high amounts of LDL and forms more oxidized LDL (ox‐LDL). Interestingly, lectin‐like ox‐LDL receptor 1 (LOX‐1), a receptor for ox‐LDL and a recognized key molecule for cardiovascular diseases, was highly expressed in tumor endothelial cells (TECs). Neutrophils are important for ox‐LDL formation. Since we observed the accumulation and activation of neutrophils in HM‐tumors, we evaluated the involvement of LOX‐1 in neutrophil migration and activation. LOX‐1 induced neutrophil migration via CCL2 secretion from TECs, which was enhanced by ox‐LDL. Finally, we show genetic manipulation of LOX‐1 expression in TECs or tumor stroma tended to reduce lung metastasis. Thus, the LOX‐1/ox‐LDL axis in TECs may lead to the formation of a high metastatic‐tumor microenvironment via attracting neutrophils.

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

Cited by 45 publications

References 35 publications

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

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

Qiliqiangxin improves oxidized low-density lipoprotein-induced human coronary artery endothelial cells injury

The oxidized‐LDL/LOX‐1 axis in tumor endothelial cells enhances metastasis by recruiting neutrophils and cancer cells

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