Ox-LDL increases OX40L in endothelial cells through a LOX-1-dependent mechanism

Dong, Qian; Xiang, Rong; Zhang, D.Y.; Qin, Shucun

doi:10.1590/1414-431x20132733

Cited by 6 publications

(4 citation statements)

References 17 publications

(17 reference statements)

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“…The mitogen-activated protein kinase/extracellular-signal-regulated kinase 1/2 signaling pathway is involved in the cytotoxic effects of ox-LDL that inhibit the proliferation of HUVECs ( 25 ). The cytotoxicity of ox-LDL in HUVECs is dependent on the LOX-1 receptor ( 26 ). Therefore rescuing EC proliferation, which represents a potential therapeutic approach for limiting the development of atherosclerosis ( 27 ), may be achieved by inhibiting the expression of LOX-1.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-98 rescues proliferation and alleviates ox-LDL-induced apoptosis in HUVECs by targeting LOX-1

Chen

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Oxidized low-density lipoprotein (ox-LDL) is a major and critical mediator of atherosclerosis, and the underlying mechanism is thought to involve the ox-LDL-induced dysfunction of endothelial cells (ECs). MicroRNAs (miRNAs), which are a group of small non-coding RNA molecules that post-transcriptionally regulate the expression of target genes, have been associated with diverse cellular functions and the pathogenesis of various diseases, including atherosclerosis. miRNA-98 (miR-98) has been demonstrated to be involved in the regulation of cellular apoptosis; however, the role of miR-98 in ox-LDL-induced dysfunction of ECs and atherosclerosis has yet to be elucidated. Therefore, the present study aimed to investigate the role of miR-98 in ox-LDL-induced dysfunction of ECs and the underlying mechanism. It was demonstrated that miR-98 expression was markedly downregulated in ox-LDL-treated human umbilical vein ECs (HUVECs) and that miR-98 promoted the proliferation and alleviated apoptosis of HUVECs exposed to ox-LDL. In addition, the results demonstrated that lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) was a direct target of miR-98 in HUVECs, as indicated by a luciferase assay. The results of the present study suggested that miR-98 may inhibit the uptake of toxic ox-LDL, maintain HUVEC proliferation and protect HUVECs against apoptosis via the suppression of LOX-1.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-98 rescues proliferation and alleviates ox-LDL-induced apoptosis in HUVECs by targeting LOX-1

Chen

Wang

et al. 2017

Experimental and Therapeutic Medicine

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“…In addition, MetS increased extracellular (Ox-LDL) and myocardial (superoxide) oxidative stress, activating LOX signaling and NADPH. 41 This in turn might have induced apoptosis via MAPK signaling, particularly p38 and ERK1/2, 42 aggravating mitochondrial damage and creating a negative cycle of mitochondrial dysfunction, oxidative stress, and apoptosis. Congruently, myocardial apoptosis observed in the early stages of experimental MetS is an important contributor to progression to cardiac dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial targeted peptides preserve mitochondrial organization and decrease reversible myocardial changes in early swine metabolic syndrome

Yuan

Woollard

Jordan

et al. 2017

Cardiovascular Research

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“…When subjected to irritative stimuli, such as hypertension or dyslipidamia, endothelial and smooth muscle cells express adhesion molecules that promote the local accumulation of ox-LDL[5, 6]. Ox-LDL that has accumulated on the surface of the inner vascular wall may stimulate the expression of many types of cytokines and trigger the development of atherosclerosis[7]. …”

Section: Introductionmentioning

confidence: 99%

MicroRNA-497 Induces Apoptosis and Suppresses Proliferation via the Bcl-2/Bax-Caspase9-Caspase3 Pathway and Cyclin D2 Protein in HUVECs

Tang

Wang

et al. 2016

PLoS ONE

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IntroductionMicroRNAs play crucial roles in various types of diseases. However, to date, no information about the role of miR-497 in the development of atherosclerosis has been reported. This study investigated the possible role of miR-497 in vascular endothelial cell injury during the early stage of atherosclerosis.Materials and MethodsThe expression level of miR-497 in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL was detected using qRT-PCR. To perform gain of function and loss of function analyses, miR-497 mimics were transfected into HUVECs, and miR-497 inhibitors were transfected into HUVECs stimulated with ox-LDL. Flow cytometry was used to analyze cell cycle progression and apoptosis. EdU and CCK-8 assays were employed to detect DNA synthesis and cell proliferation, respectively. After bioinformatics prediction, a dual Luciferase Reporter assay was used to analyze the direct target genes of miR-497. The mRNA and protein levels of the target genes were detected using qRT-PCR and western blot analyses, respectively. Caspase-9/3 activity was analyzed to determine the mechanism of endothelial dysfunction.ResultsWe showed that miR-497 was significantly upregulated in HUVECs stimulated with ox-LDL. Ectopic expression of miR-497 suppressed cell proliferation, induced apoptosis and increased the activity of caspase-9/3. After verification, Bcl2 and CCND2 were shown to be direct target genes of miR-497 in HUVECs. MiR-497 significantly suppressed cell proliferation by arresting the cell cycle through the CCND2 protein and induced apoptosis through the Bcl2/Bax-caspase9-caspase3 pathway.ConclusionOverall, our study shows that miR-497 might play a role in the development of atherosclerosis by inducing apoptosis and suppressing the proliferation of vascular endothelial cells. Therefore, miR-497 could be a potential therapeutic target for the treatment of atherosclerosis.

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Ox-LDL increases OX40L in endothelial cells through a LOX-1-dependent mechanism

Cited by 6 publications

References 17 publications

MicroRNA-98 rescues proliferation and alleviates ox-LDL-induced apoptosis in HUVECs by targeting LOX-1

MicroRNA-98 rescues proliferation and alleviates ox-LDL-induced apoptosis in HUVECs by targeting LOX-1

Mitochondrial targeted peptides preserve mitochondrial organization and decrease reversible myocardial changes in early swine metabolic syndrome

MicroRNA-497 Induces Apoptosis and Suppresses Proliferation via the Bcl-2/Bax-Caspase9-Caspase3 Pathway and Cyclin D2 Protein in HUVECs

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