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Role of PERK/eIF2α/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis 被引量:21
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作者 TAO Yong Kang YU Pu Lin +3 位作者 BAI Yong Ping YAN Sheng Tao ZHAO Shui Ping ZHANG Guo Qiang 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2016年第12期868-876,共9页
Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in th... Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis. 展开更多
关键词 PERK elF2a CHOP Endoplasmic reticulum stress oxidized low-density lipoprotein Endothelial cell Apoptosis ATHEROSCLEROSIS Caspase-3
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Influence of Oxidized Low Density Lipoprotein on the Proliferation of Human Artery Smooth Muscle Cells in vitro 被引量:5
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作者 乔晨晖 张凯伦 夏家红 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2007年第1期20-23,共4页
The effects of oxidized low density lipoprotein (ox-LDL) on the proliferation of cultured human vascular smooth muscle cells (vSMC) were investigated in vitro. By using NaBr density gradient centrifugation, LDL wa... The effects of oxidized low density lipoprotein (ox-LDL) on the proliferation of cultured human vascular smooth muscle cells (vSMC) were investigated in vitro. By using NaBr density gradient centrifugation, LDL was isolated and purified from human plasma. Ox-LDL was produced from LDL by being incubated with CuSO4. ox-LDL was then added to the culture medium at different concentrations (35, 60, 85, 110, 135 and 160μg/mL) for 7 days. The influence of ox-LDL on vSMC proliferation was observed in growth curve, mitosis index, and in situ determination of apoptosis. The data were analyzed with SPSS 10.0 software. The results showed that the ox-LDL produced in vitro had a good purity and optimal oxidative degree, which was similar to the intrinsic ox-LDL in atherosclerotic plaque, ox-LDL at a concentration of 35 μg/mL demonstrated the strongest proliferation inducement, and at a concentration of 135 μg/mL, ox-LDL could inhibit the growth of vSMC. ox-LDL at concentrations of 35 and 50 μg/mL presented powerful mitotic trigger, and with the increase of ox-LDL concentration, the mitotic index of vSMC was decreased gradually, ox-LDL at higher concentrations promoted more apoptotic vSMCs, ox-LDL at lower concentrations triggered proliferation of vSMCs, and at higher concentrations induced apoptosis in vSMCs, ox-LDL played a promotional role in the pathogenesis and development of atherosclerosis by affecting vSMC proliferation and apoptosis. 展开更多
关键词 oxidized low density lipoprotein smooth muscle cell PROLIFERATION ATHEROSCLEROSIS
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Oxidized low-density lipoprotein receptor 1:a novel potential therapeutic target for intracerebral hemorrhage 被引量:3
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作者 Hui-Yuan Zhang Xi Lu +2 位作者 Yue-Han Hao Ling Tang Zhi-Yi He 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第8期1795-1801,共7页
Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive... Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke.Therefore,OLR1 is likely involved in the progress of intracerebral hemorrhage.In this study,we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model.OLR1 small interfering RNA(10μL;50 pmol/μL)was injected into the right basal ganglia to knock down OLR1.Twenty-four hours later,0.5 U collagenase type VII was injected to induce intracerebral hemorrhage.We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma,neuron loss,inflammatory reaction,and oxidative stress in rat brain tissue.We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway.Therefore,silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage.These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage. 展开更多
关键词 ferroptosis inflammation intracerebral hemorrhage neurological behavior NEUROPROTECTION novel therapeutic target oxidative stress oxidized low-density lipoprotein receptor 1 p38 signaling pathway secondary brain injury
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A modified laser-induced choroidal neovascularization animal model with intravitreal oxidized low-density lipoprotein 被引量:2
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作者 Tong Wu Kuan-Rong Dang +6 位作者 Ya-Fen Wang Bao-Zhen Lyu Wen-Qin Xu Guo-Rui Dou Jian Zhou Yan-Nian Hui Hong-Jun Du 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2020年第8期1187-1194,共8页
AIM: To investigate whether intravitreal injection of oxidized low-density lipoprotein(OxLDL) can promote laserinduced choroidal neovascularization(CNV) formation in mice and the mechanism involved, thereby to develop... AIM: To investigate whether intravitreal injection of oxidized low-density lipoprotein(OxLDL) can promote laserinduced choroidal neovascularization(CNV) formation in mice and the mechanism involved, thereby to develop a better animal model.METHODS: C57BL6/J mice were randomized into three groups. Immediately after CNV induction with 532 nm laser photocoagulation, 1.0 μL of OxLDL [100 μg/m L in phosphate-buffered saline(PBS)] was intravitreally injected, whereas PBS and the same volume low-density lipoprotein(LDL;100 μg/m L in PBS) were injected into the vitreous as controls. Angiogenic and inflammatory cytokines were measured by quantitative real-time polymerase chain reaction(q RT-PCR) and Western blotting(WB) after 5 d, and CNV severity was analyzed by choroid flat mount and immunofluorescence staining after 1wk. In vitro, retinal pigment epithelial(RPE) cell line(ARPE19) were treated with OxLDL(LDL as control) for 8 h. Angiogenic and inflammatory cytokine levels were measured. A specific inhibitor of lectin-like oxidized low-density lipoprotein receptor 1(LOX1) was used to evaluate the role of LOX1 in this process.RESULTS: At 7 d after intravitreal injection of 1 μL(100 μg/mL) OxLDL, T15-labeled OxLDL was mainly deposited around the CNV area, and the F4/80-labeled macrophages, the CD31-labeled vascular endothelial cells number and CNV area were increased. Meanwhile, WB and qR T-PCR results showed that vascular endothelial growth factor(VEGF), CC chemokine receptor 2(CCR2), interleukin-6(IL-6), IL-1β, and matrix metalloproteinase 9(MMP9) expressions were increased, which was supported by in vitro experiments in RPE cells. LOX1 inhibitors significantly reduced expressions of inflammatory factors IL-1β and VEGF. CONCLUSION: A modified laser-induced CNV animal model is established with intravitreal injection of 1 μL(100 μg/mL) of OxLDL at 7 d, which at least partially through LOX1. This animal model can be used as a simple model for studying the role of OxLDL in age-related macular degeneration. 展开更多
关键词 age-related macular degeneration choroidal neovascularization oxidized low-density lipoprotein animal model
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Effects of Oxidized Low Density Lipoprotein on Transformation of Valvular Myofibroblasts to Osteoblast-like Phenotype 被引量:2
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作者 陈娣 沈迎念 +2 位作者 胡伟林 陈正平 李永胜 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2015年第3期362-367,共6页
In order to investigate the roles of Wnt signal pathway in transformation of cardiac valvular myofibroblasts to the osteoblast-like phenotype, the primary cultured porcine aortic valve myofibroblasts were incubated wi... In order to investigate the roles of Wnt signal pathway in transformation of cardiac valvular myofibroblasts to the osteoblast-like phenotype, the primary cultured porcine aortic valve myofibroblasts were incubated with oxidized low density lipoprotein(ox-LDL, 50 mg/L), and divided into four groups according to the ox-LDL treatment time: control group, ox-LDL 24-h group, ox-LDL 48-h group, and ox-LDL 72-h group. Wnt signal pathway blocker Dickkopf-1(DDK-1, 100 μg/L) was added in ox-LDL 72-h group. The expression of α-smooth muscle actin(α-SMA), bone morphogenetic protein 2(BMP2), alkaline phosphatase(ALP), and osteogenic transcription factor Cbfa-1 was detected by Western blotting, and that of β-catenin, a key mediator of Wnt signal pathway by immunocytochemical staining method. The Wnt/β-catenin was observed and the transformation of myofibroblasts to the osteoblast-like phenotype was examined. The expression of α-SMA, BMP2, ALP and Cbfa-1 proteins in the control group was weaker than in the ox-LDL-treated groups. In ox-LDL-treated groups, the protein expression of α-SMA, BMP2, ALP, and Cbfa-1 was significantly increased in a time-dependent manner as compared with the control group, and there was significant difference among the three ox-LDL-treated groups(P〈0.05 for all); β-catenin protein was also up-regulated in the ox-LDL-treated groups in a time-dependent manner as compared with the control group(P〈0.05), and its transfer from cytoplasm to nucleus and accumulation in the nucleus were increased in the same fashion(P〈0.05). After addition of DKK-1, the expression of α-SMA, bone-related proteins and β-catenin protein was significantly reduced as compared with ox-LDL 72-h group(P〈0.05). The Wnt/ β-catenin signaling pathway may play an important role in transformation of valvular myofibroblasts to the osteoblast-like phenotype. 展开更多
关键词 oxidized low density lipoprotein cardiac valve calcification MYOFIBROBLASTS WNT/Β-CATENIN OSTEOBLASTS
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EFFECT OF OXIDIZED-LDL ON NF-κB NUCLEAR TRANSLOCATION IN AORTIC SMOOTH MUSCLE CELLS ORIGINATED FROM RATS OF DIFFERENT AGES 被引量:2
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作者 Jun-huaZhang LiZhou Hong-chaoYin Pei-maoLiu HuaZhang Ming-pengShe 《Chinese Medical Sciences Journal》 CAS CSCD 2005年第2期112-115,共4页
Objective To investigate the molecular mechanism of atherosclerosis that related to age. Methods Immunohistochemistry staining and Western blot were adopted to determine the nuclear translocation of nuclear factor-kap... Objective To investigate the molecular mechanism of atherosclerosis that related to age. Methods Immunohistochemistry staining and Western blot were adopted to determine the nuclear translocation of nuclear factor-kappa B (NF-κB) and expression of platelet-derived growth factor B (PDGF-B) in smooth muscle cells (SMCs) co-cultured with low density lipoprotein (LDL), oxidized LDL (ox-LDL), and ox-LDL+high density lipoprotein (HDL) originated from rats of 2 and 10 months old respectively. Fat stain was used to identify the lipid intake in SMCs. Results The optimal stimulation time of ox-LDL to SMCs was 12 hours. NF-κB intensity increased in most nuclei of SMCs that originated from rats of either 2 or 10 months old co-cultured with ox-LDL. The intensity of NF-κB and the amount of intracellular lipid taken in SMCs were more obvious in cells from 10-month-old rats than from the younger ones. Change of PDGF-B expression in SMCs was not remarkable in each group of rats. Conclusions The 10-month-old rats are more susceptive to ox-LDL than 2-month-old rats in activating nuclear transloca- tion of NF-κB. Maybe this is one of the important reasons contributing to the difference between the older and younger rats on the initiation and development of atherosclerosis lesion. Expression of PDGF-B is not associated with the activity of nuclear translocation of NF-κB. 展开更多
关键词 oxidized low density lipoprotein nuclear factor-kappa B platelet-derived growth factor B smooth muscle cell
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OXIDIZED HIGH-DENSITY LIPOPROTEIN PROMOTES MATURATION AND MIGRATION OF BONE MARROW DERIVED DENDRITIC CELLS FROM C57BL/6J MICE 被引量:1
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作者 Zeng-xiang XuYong-zong Yang +5 位作者 Da-ming Feng Shuang Wang Ya-ling Tang Fan He Yan Xia Fang Li 《Chinese Medical Sciences Journal》 CAS CSCD 2008年第4期224-229,共6页
Objective To explore the influence of oxidized high-density lipoprotein (oxHDL) on the maturation and migration of bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice. Methods The C57BL/6J mice bone ma... Objective To explore the influence of oxidized high-density lipoprotein (oxHDL) on the maturation and migration of bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice. Methods The C57BL/6J mice bone marrow cell suspension was prepared and purified. Recombinant granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant interleukin-4 (rmlL-4) were used to promote monocytes to differentiate and suppress lymphocytes. Then 50μg/mL oxHDL was added to stimulate BMDCs, using 50μg/mL high-density lipoprotein (HDL) as homologous protein control, PBS as negative control, and 1 μg/mL lipopolysaccharide (LPS) as positive control. The CD86 and MHCII expression rates were detected with fluorescence-activated cell sorting (FACS). Liquid scintillation counting (LSC) was used in mixed lymphocyte reactions (MLRs) to reflect the ability of BMDCs in stimulating the proliferation of homologous T cells, Levels of cytokines IL-12 and IL-10 were detected by ELISA. The cell migration was evaluated with the transwell system. Results Compared with PBS group, the expressions of CD86 and MHCII, counts per minute of MLRs, secretion of IL-12 and IL-10, and number of migrated cells in oxHDL group and LPS group significantly increased (all P 〈 0.05), while the increment was less in oxHDL group than LPS group. The number of migrated cells in oxHDL group was about twice of that in HDL group. Conclusion OxHDL may promote the maturation and migration of BMDCs in vitro. 展开更多
关键词 dendritic cell oxidized high-density lipoprotein MATURATION MIGRATION ATHEROSCLEROSIS
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Mitofusin2 Decreases Intracellular Cholesterol of Oxidized LDL-Induced Foam Cells from Rat Vascular Smooth Muscle Cells 被引量:2
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作者 贺超 陈颖 +3 位作者 刘纯 操明 范玉璟 郭小梅 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2013年第2期212-218,共7页
Mitofusin2 (Mfn2) plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracell... Mitofusin2 (Mfn2) plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracellular cholesterol in the foam ceils derived from rat VSMCs (rVSMCs) and also to investigate the effects of Mfn2 on the expression of adenosine triphosphate-binding cassette subfamily A member 1 (ABCA1), adenosine triphosphate-binding cassette subfamily G member 1 (ABCG1) and peroxisome proliferator-activated receptor gamma (PPARy). The rVSMCs were co-cultured with oxi- dized low density lipoprotein (LDL, 80 ~tg/mL) to produce foam cells and cholesterol accumulation in cells. Before oxidized LDL treatment, different titers (20, 40 and 60 pfu/cell) of recombinant adenovirus containing Mfn2 gene (Adv-Mfn2) were added into the culture medium for 24 h to transfect the Mfn2 gene into the rVSMCs. Then the cells were harvested for analyses. The protein expression of Mfn2 was significantly higher in Adv-Mfn2-transfected group than in untransfected group (P〈0.05), and the ex- pression levels significantly increased when the titer of Adv-Mfn2 increased (P〈0.05). At 24 or 48 h af- ter oxidized LDL treatment, rVSMCs became irregular and their nuclei became larger, and their plasma abounded with red lipid droplets. However, the number of red lipid droplets was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group. At 48 h after oxidized LDL treatment, the intracellular cholesterol in rVSMCs was significantly increased (P〈0.05), but it was sig- nificantly decreased in Adv-Mfn2-transfected group as compared with untransfected group (P〈0.05), and it also significantly decreased when the titer of Adv-Mfn2 increased (P〈0.05). The mRNA and pro- tein expression levels of ABCA1 and ABCG1 were significantly increased in Adv-Mfn2-transfected group as compared with untransfected group (P〈0.05). Though the mRNA and protein expression levels of PPARy was not significantly increased (P〉0.05), the phosporylation levels of PPARy were signifi- cantly decreased in Adv-Mfn2-transfected group as compared with untransfected group (P〈0.05). These results suggest that the transfection of Adv-Mfn2 can significantly reduce intracellular cholesterol in oxidized LDL-induced rVSMCs possibly by decreasing PPAR'/phosporylation and then increasing pro- tein expression levels of ABCAI and ABCG1, which may be helpful to suppress the formation of foam cells. 展开更多
关键词 Mitofusin 2 peroxisome proliferator-activated receptor gamma adenosine triphosphatebinding cassette subfamily A member 1 adenosine triphosphate-binding cassette subfamily G member 1 vascular smooth muscle ceils oxidized low density lipoprotein rats
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Obstructive jaundice leads to accumulation of oxidized low density lipoprotein in human liver tissue 被引量:1
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作者 Mustafa Comert Yucel Ustundag +2 位作者 Ishak Ozel Tekin Banu Dogan Gun Figen Barut 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第31期5094-5095,共2页
Oxidized low density lipoprotein (ox-LDL) molecule is one of the most important modified lipoproteins produced during the oxidative stress. Modified lipoproteins have been defined as being part of the immune inflamm... Oxidized low density lipoprotein (ox-LDL) molecule is one of the most important modified lipoproteins produced during the oxidative stress. Modified lipoproteins have been defined as being part of the immune inflammatory mechanisms in association with oxidant stress. We have reported the accumulation of ox-LDL in Balb/c mice liver after bile duct ligation previously. Here, we investigated this finding in human beings with obstructive jaundice. Our study demonstrates that obstructive jaundice results in tremendous accumulation of ox-LDL in the liver tissue of patients. 展开更多
关键词 Obstructive jaundice LIVER Oxidative stress oxidized low density lipoprotein
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Oxidized low density lipoprotein (Ox-LDL) impacts on erythrocyte viscoelasticity and its molecular mechanism 被引量:1
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作者 K.-L.Paul Sung Lanping Amy Sung 《医用生物力学》 EI CAS CSCD 2009年第S1期60-60,共1页
Aim:The oxidized low-density lipoprotein(OxLDL) plays an important role in atherosclerosis yet it remains unclear if it damages circulating erythrocytes. Method: In this study。
关键词 OX-LDL impacts on erythrocyte viscoelasticity and its molecular mechanism oxidized low density lipoprotein
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Oxidized phospholipids and lipoprotein-associated phospholipase A_2 as important determinants of Lp(a) functionality and pathophysiological role 被引量:9
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作者 Alexandros D.Tselepis 《The Journal of Biomedical Research》 CAS CSCD 2018年第1期13-22,共10页
Lipoprotein(a) [Lp(a)] is composed of a low density lipoprotein(LDL)-like particle to which apolipoprotein(a)[apo(a)] is linked by a single disulfide bridge. Lp(a) is considered a causal risk factor for is... Lipoprotein(a) [Lp(a)] is composed of a low density lipoprotein(LDL)-like particle to which apolipoprotein(a)[apo(a)] is linked by a single disulfide bridge. Lp(a) is considered a causal risk factor for ischemic cardiovascular disease(CVD) and calcific aortic valve stenosis(CAVS). The evidence for a causal role of Lp(a) in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp(a) as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp(a) functionality may be played by its oxidized phospholipids(OxPL) content. Importantly, most of circulating OxPL are associated with Lp(a); however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp(a) over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp(a) is primarily driven by its OxPL content.An important role in Lp(a) functionality may be played by the lipoprotein-associated phospholipase A_2(Lp-PLA_2),an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp(a). The present review article discusses new data on the pathophysiological role of Lp(a) and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp(a). 展开更多
关键词 atherosclerosis calcific aortic valve stenosis coronary artery disease lipoprotein(a) lipoprotein-associated phospholipase A_2 oxidized phospholipids
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Oxidized low-density lipoprotein stimulates CD206 positive macrophages upregulating CD44 and CD133 expression in colorectal cancer with high-fat diet
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作者 Shi-Min Zheng Hao Chen +5 位作者 Wei-Hong Sha Xiao-Fen Chen Jian-Bin Yin Xiao-Bo Zhu Zhong-Wen Zheng Juan Ma 《World Journal of Gastroenterology》 SCIE CAS 2022年第34期4993-5006,共14页
BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC... BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC.Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment.The role of ox-LDL in CRC remains unclear.AIM To investigate the role of ox-LDL through macrophages in HFD associated CRC.METHODS The expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence.We stimulated the macrophages with 20μg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction.We further knocked down LOX-1,the surface receptor of ox-LDL,to confirm the function of ox-LDL in macrophages.Then,LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot.RESULTS The expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia,and also upregulated in the HFD-fed mice.Moreover,an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation.Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages.Ox-LDL could induce CD206+macrophages,which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells.CONCLUSION Ox-LDL stimulates CD206+macrophages to upregulate CD44 and CD133 expression in HFD related CRC. 展开更多
关键词 oxidized low-density lipoprotein CD206 positive macrophages CD44 CD133
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Aminothiols exchange in coronavirus disease 2019
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作者 Fefelova Elena Viktorovna Karavaeva Tatyana Mikhailovna +2 位作者 Parshina Anastasia Anatolyevna Ma Van De Vasilina Denisovna Tereshkov Pavel Petrovich 《Frigid Zone Medicine》 2023年第1期37-41,共5页
Objective:Clinical manifestation of the inflammatory process in its relation to biochemical markers(total cysteine[Cys],cysteine-glycine[CysGly],glutathione[GSH],glutamate-cysteine[Glu-Cys],homocysteine[Hcy],the ratio... Objective:Clinical manifestation of the inflammatory process in its relation to biochemical markers(total cysteine[Cys],cysteine-glycine[CysGly],glutathione[GSH],glutamate-cysteine[Glu-Cys],homocysteine[Hcy],the ratio of reduced to oxidized glutathione[GSH/GSSG],the ratio of reduced to oxidized cysteine[CySH/CySS],malondialdehyde-oxidized low-density lipoproteins[MDA-oxLDL])has been studied in patients with coronavirus disease 2019(COVID-19).Material and methods:48 patients with mild to severe COVID-19 and 20 healthy volunteers were included in our research.The participants were divided into 4 experimental groups according to inflammation intensity estimated based on the serum levels of interleukin 6(IL-6).Results:All 4 groups showed the prevalence of male patients and elevated serum levels of IL-6(by 54.6%).There was no comorbidity in patients with mild COVID-19(nasopharyngitis symptoms)and in healthy control subjects.50%of patients with lung damage had accompanying diseases.Alterations of aminoethyl metabolism were detected in COVID-19 patients:as reflected by the decreased levels of Cys,CysGly,and Glu-Cys and the increased levels of GSH as compared to the control group.Conclusion:Elevation of IL-6 over 7.5 pg/mL was associated with decreased GSH/GSSG and CySH/CySS ratios indicating enhanced oxidative stress and was followed by protein oxidation,specifically MDA-oxLDL. 展开更多
关键词 coronavirus disease 2019 AMINOTHIOLS oxidative stress INTERLEUKIN-6 oxidized lipoproteins
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Inhibitory Effect of Isorhapontigenin on Copper-Mediated Peroxidation of Human Low-Density Lipoprotein in vitro
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作者 方亚南 林茂 刘耕陶 《Journal of Chinese Pharmaceutical Sciences》 CAS 2004年第1期63-67,共5页
Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from... Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from sera df normal lipidemic donors was separated bysequential ultracentrifugation. The separated human IDL 1 mg·mL^(-1) in phosphate buffer saline, pH7.4, was incubated with cupric sulfate (10 μmol·L^(-1) ) at 37℃ for 10 h in the presence orabsence of various concentrations of Iso. Malondialdehyde (MDA) formation, vitamin E consumption,electrophoretic mobility of LDL, mitochondria] membrane potential of mouse peritoneal macrophages,phagocytosis of neutral red, and release of nitric oxide (NO) from macrophages were determined byvarious methods. Results Iso 1 - 100 μmol·L^(-1) significantly inhibited the increase of MDAformation, vitamin E consumption and electrophoretic mobility of LDL induced by Cu^(2+) in aconcentration-dependent manner. The injury of the mitochondrial membrane potential of mouseperitoneal macrophages due to incubation with ox-LDL (0.1 mg·mL^(-1)) at 37℃ for 12 h was markedlyprotected by 10 μmol·L^(-1) Iso. After pretreat-ment of the macrophages with 10 μmol · L^(-1)of Iso and then exposure to ox-LDL for 4 h, the reduction of phagocytosis of neutral red and releaseof NO in response to lipopolysaccharide (IPS) stimulation were significantly prevented. ConclusionIso has protective action against Cu^(2+) - mediated LDL peroxidation and ox-LDL induced toxicity tomacrophages in vitro. 展开更多
关键词 ISORHAPONTIGENIN low-density lipoprotein oxidized low-density lipoprotein MACROPHAGES PHAGOCYTOSIS mitochondrial membrane potential
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Fucoxanthin suppresses OxLDL-induced inflammation via activation of Nrf2 and inhibition of NF-κB signaling 被引量:2
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作者 Peramaiyan Rajendran Abdullah M AlZahrani 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2022年第5期207-215,共9页
Objective:To explore the impact of fucoxanthin on oxidized low-density lipoprotein(OxLDL)-induced stress and inflammation in human endothelial cells and its underlying mechanisms.Methods:HUVECs were treated with OxLDL... Objective:To explore the impact of fucoxanthin on oxidized low-density lipoprotein(OxLDL)-induced stress and inflammation in human endothelial cells and its underlying mechanisms.Methods:HUVECs were treated with OxLDL and/or fucoxanthin for a range of time points and concentrations.We evaluated the effects of fucoxanthin on OxLDL-induced HUVECs using the MTT assay,reactive oxygen species accumulation assay,ELISA,RT-PCR,immunofluorescence,and Western blotting.Results:Fucoxanthin enhanced the cell viability in a dose dependent manner after OxLDL exposure.Furthermore,fucoxanthin pretreatment significantly decreased OxLDL-induced reactive oxygen species production and prevented the activation of the nuclear factor kappa-B pathway,which led to substantial suppression of pro-inflammatory gene expressions.OxLDL-induced upregulation of interleukin-6,intercellular adhesion molecule-1,vascular cell adhesion molecule-1,interleukin-1β,monocyte chemotactic protein-1,cyclooxygenase-1,and tumor necrosis factor-αwas significantly reduced by fucoxanthin.Conclusions:Fucoxanthin can inhibit OxLDL-induced vascular inflammation and oxidative stress in HUVECs by targeting Nrf2 signaling pathways. 展开更多
关键词 oxidized low-density lipoprotein FUCOXANTHIN Atherosclerosis INFLAMMATION Oxidative stress Cell viability HUVEC Nrf2 signaling pathway NF-ΚB
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Atorvastatin attenuates oxidative stress in Alzheimer's disease
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作者 Cai Zhiyou Yan Yong Wang Yonglong 《Journal of Medical Colleges of PLA(China)》 CAS 2008年第1期31-37,共7页
Objective: To investigate serum level of SOD, MDA, ox-LDL, AchE and Ach in AD, to study atorvastatin influence on serum level of SOD, MDA, ox-LDL, Ache and Ach in AD and its neuroprotection mechanisms. Methods Subjec... Objective: To investigate serum level of SOD, MDA, ox-LDL, AchE and Ach in AD, to study atorvastatin influence on serum level of SOD, MDA, ox-LDL, Ache and Ach in AD and its neuroprotection mechanisms. Methods Subjects were divided into: normal blood lipid level group with Alzheimer's disease (A), higher blood lipid level group with Alzheimer's disease (AH), normal blood lipid level Alzheimer's disease group with atorvastatin treeatment (AT), higher blood lipid level Alzheimer's disease group with atorvastatin treeatment(AHT). Ox-LDL was measured by enzyme linked immunosorbent assay; SOD, MDA, ox-LDL, AchE, Ach and blood lipid level in AD was measured by biochemistry. Results: The serum level of MDA, Ache in AH group after atorvastatin treatment is lower ;The serum level of SOD, Ach in AH group is more increased than that of in A group; The serum level of ox-LDL in AH, A groups is lower than that of in A group; The dementia degree is lower after atorvastatin treatment. Conclusion: Atorvastatin can decrease serum level of MDA, AchE and ox-LDL, and increase that of SOD, Ach, and attenuate dementia symptom in AD, especially, with hyperlipemia. The hypothesis of atorvastatin neuroprotection is concluded that atorvastatin may restrain free radical reaction and retard oxidation in AD. 展开更多
关键词 ATORVASTATIN Alzheimer's disease Superoxide dismutase Matondialdehyde oxidized low-density lipoprotein
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Activation of Proteinkinase ERK Mediates Induction of Macrophage MMP-12 by OxLDL
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作者 HeChun-yan ZhouXin +2 位作者 LiXiao-ming YuHong HongJia-ling 《Wuhan University Journal of Natural Sciences》 EI CAS 2004年第1期120-124,共5页
The present study was undertaken to investigate the effect of oxidized low density lipoprotein (oxLDL) on the expression of macrophage matrix metalloproteinase-12 (MMP-12), and the possible mechanisms. Activation of e... The present study was undertaken to investigate the effect of oxidized low density lipoprotein (oxLDL) on the expression of macrophage matrix metalloproteinase-12 (MMP-12), and the possible mechanisms. Activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was detected by Western blot Analysis. Enzymatic activity of MMP-12 was determined by β-casein zymography. RT-PCR analysis was used to measure the mRNA expression level of MMP-12. OxLDL-stimulated macrophages produced increased casein-degrading activities and oxLDL also significantly increased the mRNA level of MMP-12 in a dose-dependent manner. OxLDL stimulated the phosphorylation of ERK1/2 in macrophages. The use of the specific inhibitor indicated that the ERK1/2 signaling pathway was required for the induction of MMP-12. These data demonstrated that oxLDL induced MMP-12 expression in macrophages through an ERK1/2-dependent pathway. Key words oxidized low density lipoproteins - macrophage - matrix metalloproteinases CLC number Q 556+.9 Foundation item: Supported by the Natural Science Foundation of Hubei Province (99J138)Biography: He Chun-yan (1970-), female, Ph. D candidate, research direction: biochemistry diagnosis of atherosclerosis. 展开更多
关键词 oxidized low density lipoproteins MACROPHAGE matrix metalloproteinases
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Effects of IGF-1 and oxLDL on expression of phosphatase PHLPP1 in vascular smooth muscular cells
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作者 Xing-Li Wu Ding-You Yang Zhong-Su Yang De-Yin Li Hui-Bin Xu Shi-Wen Wang 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2009年第4期237-240,共4页
Objective To investigate the effects of insulin-like growth factor-1 (IGF-1) and oxidized low density lipoprotein (oxLDL) on expression ofphosphatase PHLPP 1 in vascular smooth muscle cells (VSMCs). Methods Rabb... Objective To investigate the effects of insulin-like growth factor-1 (IGF-1) and oxidized low density lipoprotein (oxLDL) on expression ofphosphatase PHLPP 1 in vascular smooth muscle cells (VSMCs). Methods Rabbit aortic VSMCs were cultured. VSMCs proliferation ability was determined by measuring cell number and mitochondrial dehydrogenase (MD) activity with MTT assay. Western blot was used to detect the protein expression ofphosphatase PHLPP1. Results IGF-1 (100ug/L) increased cell number and MD activity to 3.02 and 3.59 times of that in control group, oxLDL(501xg/ml) elevated the above two parameters to 2.03 and 2.91 times respectively. Western blot showed that IGF-1 and oxLDL inhibited the expression of PHLPPI to 39.27% and 40.26% of the control group (P〈0.01 ). Conclusion IGF- 1 and oxLDL may enhance the proliferation of VSMCs by decreasing the expression ofphosphatase PHLPP 1. 展开更多
关键词 PH domain leucine-rich repeat protein phosphatasel (PHLPP1) insulin-like growth factor-l oxidized low density lipoprotein(oxLDL) vascular smooth muscle cells
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OxLDL-induced Cytotoxicity and Its Inhibition by API_(0134) in Cultured Porcine Aortic Endothelial Cells
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作者 王宏伟 赵华月 马宝瑕 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 1996年第4期198-199,202,共3页
Protective effects of API0134 on endotheliai cells (EC) damaged by oxidatively modified low density lipoprotein (oxLDL) were studied. The results showed that the content of endothelia (ET) and malondialdehyde (MDA) in... Protective effects of API0134 on endotheliai cells (EC) damaged by oxidatively modified low density lipoprotein (oxLDL) were studied. The results showed that the content of endothelia (ET) and malondialdehyde (MDA) in the media of porcine aortic EC incubated with oxLDL were increased and the cGMP was decreased significantly, and the activity of superoxide dismutase (SOD) was inhibited. The effect of cytotoxicity of oxLDL can be eliminated by API0134.These results suggest that API0134 may protect EC against damages elicited by oxLDL. 展开更多
关键词 API_(01134) oxidatively modified low density lipoprotein endothelial cell
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Atherosclerosis and the Cholesterol Theory: A Reappraisal
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作者 Ang Peng Wong Abdul Latiff Mohamed Aleksandra Niedzwiecki 《World Journal of Cardiovascular Diseases》 2016年第11期391-409,共20页
Atherosclerosis is the precedent to ischemic heart disease, which may lead to angina, myocardial infarct, or heart failure;or to ischemic cerebrovascular disease, which may lead to stroke. The prevailing belief underl... Atherosclerosis is the precedent to ischemic heart disease, which may lead to angina, myocardial infarct, or heart failure;or to ischemic cerebrovascular disease, which may lead to stroke. The prevailing belief underlying conventional approaches to treatment of atherosclerosis and its sequel is that a diet high in cholesterol and saturated fat is the main contributory factor, triggering cholesterol build up in the intima of the blood vessels. Over the last 60 years, the blame has shifted from fats, to saturated fats, to low-density lipoprotein (LDL), and finally to oxidized LDL (Ox-LDL). Therapy has been predominantly aimed at lowering cholesterol and control of risk factors. However, there is an alternative hypothesis about the cause of heart disease linking it to the weakening of the vascular collagen matrix at the sites of high hemodynamic stress (coronary arteries) which triggers the infiltration of lipoprotein(apo) [Lp(a)] and plaque development. Accordingly, the vascular deposition of large molecules such as Lp(a) and atherosclerosis is the result of the body’s endogenous protective mechanism to reinforce the weakened artery walls. Understanding this mechanism may guide the natural prevention of this disease and form the basis for developing effective therapeutic strategies aiming at natural reversal of atherosclerosis through the reinforcement of the vascular wall structure as its primary goal. This reappraisal of atherosclerosis and the cholesterol theory looked at the historical development of the theory, and the Rath and Pauling unified theory of cardiovascular disease. 展开更多
关键词 ATHEROSCLEROSIS Low-Density Lipoprotein oxidized Low-Density Lipoprotein APOLIPOPROTEIN
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