Oxidized low density lipoprotein receptor-1 mediates oxidized low density lipoprotein-induced apoptosis in human umbilical vein endothelial cells: Role of reactive oxygen species

Chen, Xiuping; Xun, Keli; Wu, Qin; Zhang, Tiantai; Shi, Jingshan; Du, Guanhua

doi:10.1016/j.vph.2007.01.004

Cited by 108 publications

(89 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SOD (49). In the present study, ox-HDL led to a significant increase in NADPH oxidase activity and a decrease in the SOD activity, with concomitant increased production of ROS and MDA, which were mimetic to ox-LDL treatment.…”

Section: Hdl From Ms Patients Induces Oxidative Stress and Chop-mediasupporting

confidence: 59%

Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway

Yao¹,

Tian²,

Zhao³

et al. 2017

Journal of Lipid Research

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org Atherosclerosis, one of the prime causes of heart attack and stroke, has been well known as a lipid-driven inflammatory disease characterized by macrophage accumulation in subendothelial space. Apoptosis of macrophage-derived foam cells, especially in advanced atherosclerotic lesions where phagocytic clearance of dead and dying cells is defective, results in acellular necrotic lesions that are prone to plaque rupture and thrombosis formation, leading to the majority of acute vascular events (1). Thus, deeper understanding of the mechanisms of macrophage apoptosis may pave the way for developing novel therapeutic strategies to effectively prevent atherosclerotic plaque rupture and subsequent clinical complications (2). Oxidized LDL (ox-LDL) has been recognized as a major inducer, promoting foam cell formation and apoptosis in macrophages (3). In contrast, HDL exerts antiatherogenic functions such as promoting reverse cholesterol transport, suppressing inflammation, inhibiting LDL oxidation, and increasing endothelial nitric oxide production (4). However, accumulating evidence suggests that HDL, like LDL, is also susceptible to oxidative modification. Oxidized HDL Abstract Oxidized HDL (ox-HDL), unlike native HDL that exerts antiatherogenic effects, plays a proatherogenic role. However, the underlying mechanisms are not completely understood. This study was designed to explore the inductive effect of ox-HDL on endoplasmic reticulum (ER) stress-CCAAT-enhancer-binding protein homologous protein (CHOP)-mediated macrophage apoptosis and its upstream mechanisms. Our results showed that ox-HDL could be ingested by macrophages, causing intracellular lipid accumulation. As with tunicamycin (an ER stress inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2, and upregulation of glucose-regulated protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and CHOP gene silencing. Additionally, diphenyleneiodonium (DPI, an oxidative stress inhibitor), probucol (a reactive oxygen species scavenger), and toll-like receptor 4 (TLR4) silencing reduced ox-HDL-induced macrophage apoptosis, oxidative stress, and CHOP upregulation. Moreover, HDL isolated from patients with metabolic syndrome induced macrophage apoptosis, oxidative stress, and CHOP upregulation, which were blocked by PBA and DPI. These data indicate that ox-HDL may activate ER stress-CHOP-induced apoptotic pathway in macrophages via enhanced oxidative stress and that this pathway may be mediated by TLR4.

show abstract

Section: Hdl From Ms Patients Induces Oxidative Stress and Chop-mediasupporting

confidence: 59%

Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway

Yao¹,

Tian²,

Zhao³

et al. 2017

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…In contrast to the ability of small concentrations of oxLDL to stimulate tube formation, higher concentrations of oxLDL (10, 20, 40 g/mL) were noted to inhibit cell growth and cause cell injury in accordance with previous observations. [21][22][23][24] We also used native-LDL as a negative control, and found that native LDL (5 g/mL) had no effect on tube formation. Based on these findings, we chose the maximum effective concentration of oxLDL (5 g/mL) for subsequent experiments.…”

Section: Results Oxldl and Tube Formationmentioning

confidence: 99%

“…9 -15,21-25,32,33 Almost all of these studies have shown adverse effect of oxLDL, including cell apoptosis and death. 11,12,24,32,33 Unfortunately, the concentration of oxLDL used in these studies has varied from 10 to 100 g/mL. Although the precise concentration of oxLDL in the tissues is not known, these concentrations are at least 1-log higher than those seen in normal human sera.…”

Section: Discussionmentioning

confidence: 99%

“…12,24,25,38 It is interesting that the pathway leading to oxLDL-induced cell injury appears to be the same that leads to angiogenic response to small concentrations of oxLDL. 24,38 The only difference seems to be the generation of large amounts of ROS when high concentrations of oxLDL are used. Chen et al 22,23 showed that high concentrations of oxLDL downregulate basic fibroblast growth factor in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…In keeping with previously published data, 18 we observed that LOX-1 expression increased in response to oxLDL in a concentration-dependent fashion (Figure 2A). Activation of LOX-1 itself can stimulate the formation of ROS, 10,24 and NADPH oxidase activation is a major source of ROS in endothelial cells. 20 We therefore measured intracellular ROS generation and NADPH oxidase expression in HCAECs treated with oxLDL, and observed that oxLDL enhanced ROS generation and expression of NADPH oxidase (gp91 phox and p47 phox subunits).…”

Section: Oxldl and Redox-sensitive Signaling Eventsmentioning

confidence: 99%

See 2 more Smart Citations

Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

Dandapat

Sun

et al. 2007

ATVB

139

116

View full text Add to dashboard Cite

Objective-Vascular endothelial growth factor (VEGF), a key angiogenic growth factor, stimulates angiogenesis. Low levels of reactive oxygen species (ROS) function as signaling molecules for angiogenesis. We postulated that low concentrations of oxLDL might induce low levels of ROS and initiate angiogenesis. Methods and Results-An in vitro model of tube formation from human coronary artery endothelial cells (HCAECs) was used.oxLDL (0.1, 1, 2, 5 g/mL) induced VEGF expression and enhanced tube formation. oxLDL-mediated VEGF expression and tube formation were suppressed by a specific blocking anti-LOX-1 antibody. Anti-LOX-1 antibody also reduced oxLDL-induced increase in the expression of NADPH oxidase (gp91 phox and p47 phox subunits) and subsequent intracellular ROS generation, phosphorylation of p38 as well as p44/42MAPK, and NF-B p65 expression. gp91 phox siRNA had a similar effect. The expression of VEGF and NF-B p65 induced by oxLDL was also inhibited by the specific extracellular signal-regulated kinase (ERK) 1/2 inhibitor U0126 and the p38 MAPK inhibitor SB203580. Importantly, the NADPH oxidase inhibitor apocynin, gp91 phox siRNA, U0126, and SB203580 all reduced tube formation in response to oxLDL. Conclusions-These

show abstract

Beneficial effects of (−)‐epigallocatechin‐3‐O‐gallate on diabetic peripheral neuropathy in the rat model

Abo-Salem

Ali

Harisa

et al. 2020

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Diabetic neuropathic pain is characterized by spontaneous pain with hyperalgesia and allodynia. We investigated whether (−)‐epigallocatechin‐3‐O‐gallate could improve diabetic neuropathic pain development through hypoglycemic, hypolipidemic, antioxidant, and anti‐inflammatory effects. Diabetes was induced in rats by streptozotocin (55 mg/kg/once) and treated with (−)‐epigallocatechin‐3‐O‐gallate (25 mg/kg/orally/once/daily/5 weeks). Diabetic rats showed an increase in serum levels of glucose, nitric oxide, triglyceride, total cholesterol, and low‐density lipoprotein‐cholesterol with a decrease in high‐density lipoprotein‐cholesterol and body weight. Also, there was an elevation in brain malondialdehyde with a marked reduction in brain levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione‐S‐transferase. Furthermore, diabetic rats showed a clear reduction in plasma levels of insulin and an increase in plasma cytokines (interleukin‐6 and tumor necrosis factor‐α). Moreover, diabetic rats exhibited hyperalgesia as indicated by a hot plate, tail immersion, formalin, and carrageenan‐induced edema tests as well as brain histopathological changes (neuron degeneration, gliosis, astrocytosis, congestion and hemorrhage). (−)‐Epigallocatechin‐3‐O‐gallate treatment ameliorated alterations in body weight, biochemical parameters, pain sensation, and histopathological changes in brain tissue. (−)‐Epigallocatechin‐3‐O‐gallate offers promising hypoglycemic, hypolipidemic, antioxidant and anti‐inflammatory effects, which can prevent the development and progression of diabetic neuropathic pain.

show abstract

Oxidized low density lipoprotein receptor-1 mediates oxidized low density lipoprotein-induced apoptosis in human umbilical vein endothelial cells: Role of reactive oxygen species

Cited by 108 publications

References 31 publications

Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway

Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway

Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

Beneficial effects of (−)‐epigallocatechin‐3‐O‐gallate on diabetic peripheral neuropathy in the rat model

Contact Info

Product

Resources

About