Role of PERK/eIF2α/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis

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.

Oxidized low-density lipoprotein receptor 1:a novel potential therapeutic target for intracerebral hemorrhage

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.

Anti-oxidized low-density lipoprotein antibodies in chronic heart failure

Oxidative stress may play a significant role in the pathogenesis of heart failure(HF).Antibodies to oxidized low-density lipoprotein(oxLDL Abs) reflect an immune response to LDL over a prolonged period and may represent long-term oxidative stress in HF.The oxLDL plasma level is a useful predictor of mortality in HF patients,and measurement of the oxLDL Abs level may allow better management of those patients.Antibodies to oxLDL also significantly correlate with the New York Heart Association score.Hypercholesterolemia,smoking,hypertension,and obesity are risk factors for atherosclerotic coronary heart disease(CHD) leading to HF,but these factors account for only onehalf of all cases,and understanding of the pathologic process underlying HF remains incomplete.Nutrients with antioxidant properties can reduce the susceptibility of LDL to oxidation.Antioxidant therapy may be an adjunct to lipid-lowering,angiotensin converting enzyme inhibition and metformin(in diabetes) therapy for the greatest impact on CHD and HF.Observational data suggest a protective effect of antioxidant supple-mentation on the incidence of HD.This review summarizes the data on oxLDL Abs as a predictor of morbidity and mortality in HF patients.

A modified laser-induced choroidal neovascularization animal model with intravitreal oxidized low-density lipoprotein

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.

Oxidized low-density lipoprotein stimulates CD206 positive macrophages upregulating CD44 and CD133 expression in colorectal cancer with high-fat diet

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.

Inhibitory Effect of Isorhapontigenin on Copper-Mediated Peroxidation of Human Low-Density Lipoprotein in vitro

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.

Lectin-like oxidized low-density lipoprotein receptor-1:protein,ligands,expression and pathophvsiological significance

Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED （1997-2006） online resources using the key term LOX-1. Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. Results The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed. Conclusions Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.

Inhibitory Effects of Simvastatin on Oxidized Low-Density Lipoprotein-lnduced Endoplasmic Reticulum Stress and Apoptosis in Vascular Endothelial Cells

Background：Oxidized low-density lipoprotein （ox-LDL）-induced oxidative stress and endothelial apoptosis are essential for atherosclerosis. Our previous study has shown that ox-LDL-induced apoptosis is mediated by the protein kinase RNA-like endoplasmic reticulum kinase （PERK）/eukaryotic translation initiation factor 2α-subunit （eIF2α）/CCAAT/enhancer-binding protein homologous protein （CHOP） endoplasmic reticulum （ER） stress pathway in endothelial cells. Statins are cholesterol-lowering drugs that exert pleiotropic effects including suppression of oxidative stress. This study aimed to explore the roles of simvastatin on ox-LDL-induced ER stress and apoptosis in endothelial cells.Methods：Human umbilical vein endothelial cells （HUVECs） were treated with simvastatin （0.1, 0.5, or 2.5 μmol/L） or DEVD-CHO （selective inhibitor of caspase-3, 100 μmol/L） for 1 h before the addition of ox-LDL （100 μg/ml） and then incubated for 24 h, and untreated cells were used as a control group. Apoptosis, expression of PERK, phosphorylation of eIF2α, CHOP mRNA level, and caspase-3 activity were measured. Comparisons among multiple groups were performed with one-way analysis of variance （ANOVA） followed by post hoc pairwise comparisons using Tukey’s tests. A value of P 〈 0.05 was considered statistically significant.Results：Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis （31.9% vs. 4.9%, P 〈 0.05）. Simvastatin （0.1, 0.5, and 2.5 μmol/L） led to a suppression of ox-LDL-induced apoptosis （28.0%, 24.7%, and 13.8%, F = 15.039, all P 〈 0.05, compared with control group）. Ox-LDL significantly increased the expression of PERK （499.5%, P 〈 0.05） and phosphorylation of eIF2α （451.6%, P 〈 0.05）, if both of which in the control groups were considered as 100%. Simvastatin treatment （0.1, 0.5, and 2.5 μmol/L） blunted ox-LDL-induced expression of PERK （407.8%, 339.1%, and 187.5%, F = 10.121, all P 〈 0.05, compared with control group） and phosphorylation of eIF2α （407.8%, 339.1%, 187.5%, F = 11.430, all P 〈 0.05, compared with control group）. In contrast, DEVD-CHO treatment had no significant effect on ox-LDL-induced expression of PERK （486.4%） and phosphorylation of eIF2α （418.8%）. Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment.Conclusions：This study suggested that simvastatin could inhibit ox-LDL-induced ER stress and apoptosis in vascular endothelial cells.

Danshen protects endothelial progenitor cells from oxidized low-density lipoprotein induced impairment

In this study, we examined the protective effects of Danshen both on endothelial progenitor cells （EPCs） in patients with hypercholesterolemia and on in-vitro EPCs of healthy volunteers. In the clinical study, we randomly divided 24 subjects with hypercholesterolemia into two groups （the control group and the Danshen-treated group）. At the end of two weeks of treatment, the EPC cellular functions of both groups were tested. The results indicated that, compared to the control group, EPCs in the Danshen-treated group showed significantly better cellular functions, which was manifested in the cloning number, the proliferation capacity, the number of EPC adhesions, and cell migration. In the subsequent in-vitro experiments, EPCs were treated with vehicle, oxidized low-density lipoprotein （Ox-LDL, 100 pg/ml）, or Ox-LDL （100 pg/ml） plus different concentrations of Danshen （Danshensu 2, 10, or 50 pg/ml, respectively） for 24 h. The results showed that Danshen treatments can prevent the detrimental effects of Ox-LDL on EPC cellular functions measured by proliferation capacity （0.24±0.08, 0.37±0.11, 0.30±0.04 vs. 0.13±0.02, P〈0.05, P〈0.01, and P〈0.01, respectively）, and adhesion ability （63.00_±11.60, 70.00±10.80, 85.50±11.41 vs. 40.50±6.85, all P〈0.01）. Compared to the group treated with Ox-LDL alone, Danshen treatment significantly decreased the lipid peroxidation end product malondialdehyde （MDA） [（4.34±0.54）, （3.98±0.47）, （3.46±0.31） vs. （5.57-±0.64） nmol/ml, all P〈0.01], increased the production of superoxide dismutase （SOD） [（29.74±0.71）, （31.09±0.83）, （30.41±0.65） vs. （14.76±3.99） U/ml, all P〈0.01], and lowered the expression of interleukin-6 （IL-6） [（24.62±7.69）, （27.04±3.14）, （33.38±18.86） vs. （230.67±33.53） pg/ml, all P〈0.01] and tumor necrosis factor-α （TNF-α） [（41.72±6.10）, （17.02±6.82）, （3.73±2.26） vs. （228.71±41.53） pg/ml, all P〈0.01] in Ox-LDL treated EPCs. These results suggest that Danshen may exert a protective effect through its antioxidant and anti-inflammatory features.

Metformin improved oxidized low-density lipoprotein-impaired mitochondrial function and increased glucose uptake involving Akt-AS160 pathway in raw264.7 macrophages

Background:Macrophage accumulation in the vascular wall is a hallmark of atherosclerosis.Studies showed that shifting of oxidized lipids-induced inflammatory macrophages towards an anti-inflammatory phenotype by promoting oxidative metabolism attenuated atherosclerosis progression.Therefore,this study aimed to investigate whether metformin,which has ameliorated atherosclerosis in animal models and clinical trials,modulated oxidized low-density lipoprotein (Ox-LDL) induced inflammatory status in macrophages by regulating cellular oxidative metabolism.Methods:Murine raw264.7 macrophages were incubated with Ox-LDL (50 μg/mL) in the presence or absence of metformin (15 μmol/L) for 24 h.Real-time polymerase chain reaction was used to quantify the transcription of classically activated (M1) proinflammatory and alternatively activated (M2) anti-inflammatory markers and mitochondrial DNA copy numbers.Cellular reactive oxygen species (ROS) production and mitochondrial membrane potential were detected by immunofluorescence.Cellular adenosine triphosphate (ATP) synthesis,glucose uptake,and lactic acid production were measured by commercial kit and normalized to cellular lysates.Western blotting analysis was performed to detect the expression of mitochondrial fusion/fission related proteins,enzymes mediating lipid metabolism and signaling pathway of glucose transport.Differences between groups were analyzed using one-way analysis of variance.Results:Metformin improved Ox-LDL-impaired anti-inflammatory phenotype in raw264.7 macrophages as shown by up-regulated transcription of anti-inflammatory markers including interleukin 10 (0.76 ± 0.04 vs.0.94 ± 0.01,P =0.003) and Resistin-like molecule alpha (0.67 ± 0.08 vs.1.78 ± 0.34,P =0.030).Conversely,Ox-LDL-diminished phosphorylation of Akt was up regulated by metformin treatment (0.47 ± 0.05 vs.1.02 ± 0.08,P =0.040),associated with an improvement of mitochondrial function,characterized by decreased ROS generation (2.50 ± 0.07 vs.2.15 ± 0.04,P =0.040),increased lipid oxidation,and elevated cellular ATP production (0.026 ± 0.001 vs.0.035 ± 0.003,P =0.020).Moreover,metformin-mediated Akt activation increased Akt substrate of 160 kDa (AS160) phosphorylation (0.51 ± 0.04 vs.1.03 ± 0.03,P =0.0041),promoted membrane translocation of glucose transporter 1,and increased glucose influx into the cells (4.78 ± 0.04 vs.5.47 ± 0.01,P < 0.001).Contusion:This study suggested that targeting macrophage metabolism with new or existing drugs had therapeutic potential for the prevention and treatment of diabetes-accelerated atherosclerosis.

Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients

Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein （HDL） reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein （ox-LDL） and anti-ox-LDL, and paraoxonase-1 （PON-1） activity in HD （n=33） and Tx （n=71） patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I （apoA-I） and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios （total cholesterol （TC）/HDL-C, LDL-C/HDL-C, triglyceride （TG）/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL） were atherogenic. The Spearman＇s rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level （R=0.363, P=0.004）, and negatively with TC （R=-0.306, P=0.012）, LDL-C （R=-0.283, P=0.020）, and non-HDL-C （R=-0.263, P=0.030） levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and de- creased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-13-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.

Aqueous Extracts of Tribulus terrestris Protects Against Oxidized Low-Density Lipoprotein-Induced Endothelial Dysfunction

Objective： To investigate the role of aqueous extracts of Tribulus terrestris （TT） against oxidized low-density lipoprotein （ox-LDL）-induced human umbilical vein endothelial cells （HUVECs） dysfunction in vitro. Methods： HUVECs were pre-incubated for 60 min with TT （30 and 3 μg/mL respectively） or 105 mol/L valsartan （as positive controls） and then the injured endothelium model was established by applying 100 μg/mL ox-LDL for 24 h. Cell viability of HUVECs was observed by real-time cell electronic sensing assay and apoptosis rate by Annexin V/PI staining. The cell migration assay was performed with a transwell insert system. Cytoskeleton remodeling was observed by immunofluorescence assay. The content of endothelial nitric oxide synthase （eNOS） was measured by enzyme-linked immunosorbent assay. Intracellular reactive oxygen species （ROS） generation was assessed by immunofluorescence and flow cytometer. Key genes associated with the metabolism of ox-LDL were chosen for quantitative real-time polymerase chain reaction to explore the possible mechanism of TT against oxidized LDL-induced endothelial dysfunction. Results： TT suppressed ox-LDL-induced HUVEC proliferation and apoptosis rates significantly （41.1% and 43.5% after treatment for 3 and 38 h, respectively; P〈0.05）. It also prolonged the HUVEC survival time and postponed the cell＇s decaying stage （from the 69th h to over 100 h）. According to the immunofluorescence and transwell insert system assay, TT improved the endothelial cytoskeletal network, and vinculin expression and increased cell migration. Additionally, TT regulated of the synthesis of endothelial nitric oxide synthase and generation of intracellular reactive oxygen species （P〈0.05）. Both 30 and 3μg/mL TT demonstrated similar efficacy to valsartan. TT normalized the increased mRNA expression of PI3Kα and Socs3. It also decreased mRNA expression of Aktl, AMPKα, JAK2, LepR and STAT3 induced by ox-LDL. The most notable changes were JAK2, LepR, PI3Kα, Socs3 and STAT3. Conclusions： TT demonstrated potential lowering lipid benefits, anti-hypertension and endothelial protective effects. It also suggested that the JAK2/STAT3 and/or PI3K/AKT pathway might be a very important pathway which was involved in the pharmacological mechanism of TT as the vascular protective agent.

Protective Effect of Propyl Gallate Against Oxidized Low-Density Lipoprotein-Induced Injury of Endothelial Cells

Objective： To evaluate the protective effect of propyl gallate （PG）, an alkyl ester of gallic acid which is an active ingredient of Radix Paeoniae, against oxidized low-density lipoprotein （ox-LDL）-induced apoptosis and death in endothelial cells （ECs） and to find out its preliminary mechanism. Methods： The cultured endothelial cells were divided into normal, model （ox-LDL）, control （fetal bovine serum）, PG high dose （20 p,g/mL）, PG middle dose （10 μg/mL）, and PG low dose （5 μg/mL） groups, each derived from three different pools of umbilical cords. The model of injured human umbilical vein endothelial cells （HUVECs） was induced by ox-LDL. The 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tetrazolium bromide （MTT） assay, Hoechst 33258 staining, flow cytometry and measurement of nitrogen monoxidum （NO） release were used to evaluate the protective effect of PG against ox-LDL-induced apoptosis and death in HUVECs. To find out the mechanism of this protective effect, the expression of endothelial nitric oxide synthase （eNOS） mRNA, eNOS protein expression, immunofluorescence of intracellular reactive oxygen species （ROS） and activities of malondialdehyde （MDA）, superoxidedismutase （SOD） and glutathione peroxidase （GPx） were observed. Results： PG significantly reduced ox-LDL-induced apoptosis and cell death. The percentage of cells death and apoptosis was significantly higher in the ox-LDL group than that in the control group （P〈0.05）. Compared with the control group, the cells death and apoptosis of PG group was no different （P〉0.05）. As compared with the ox-LDL group, results of the PG high dose group showed that cell viability was significantly increased （P〈0.05）, the level of NO release, expression of eNOS mRNA, densitometric value of eNOS protein expression, as well as the activities of SOD and GPx were all significantly higher （all P〈0.05）. Conclusion： PG could potentially serve as a novel endothelial protective agent against ox-LDL-induced injury of endothelial cell.

Atorvastatin attenuates oxidative stress in Alzheimer's disease

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.

Oxidative alterations in sickle cell disease: Possible involvement in disease pathogenesis

Sickle cell disease(SCD) is the first molecular disease in the literature. Although the structural alteration and dysfunction of the sickle hemoglobin(HbS) are well understood, the many factors modifying the clinical signs and symptoms of the disease are under investigation. Besides having an abnormal electrophoretic mobility and solubility, HbS is unstable. The autooxidation rate of the abnormal HbS has been reported to be almost two times of the normal. There are two more components of the oxidative damage in SCD: Free radical induced oxidative damage during vaso-occlusion induced ischemia-reperfusion injury and decreased antioxidant capacity in the erythrocyte and in the circulation. We will discuss the effects of oxidative alterations in the erythrocyte and in the plasma of SCD patients in this review.

The lack of association between different LDL-C levels and oxidized LDL in patients with type 2 diabetes

Background:High concentrations of low-density lipoprotein cholesterol(LDL-C)have been a known risk factor for cardiovascular diseases.Also,the role of oxidized LDL(ox-LDL)in forming atherosclerosis plaque has been proven.However,it has not yet been proven that atherogenic LDL-C byproducts like ox-LDL will decrease by keeping the LDL levels at the desired level.This study aimed to examine the relationship between LDL-C and ox-LDL in different LDL-C values in patients with type 2 diabetes(T2D).Methods:In this cross-sectional study,347 patients with T2D who received statins were enrolled.LDL-C values were defined into four groups as LDLC<55 mg/dL,55 mg/dL≤to<70 mg/dL,70 mg/dL≤to<100 mg/dL and LDLC≥100 mg/dL.Total cholesterol,triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and ox-LDL were studied in the four defined groups.Results:Ox-LDL levels were not different among the four groups(p=0.30).In addition,LDL-C and ox-LDL levels had no significant correlation(r=0.480,p=0.376).Additionally,based on this study analysis,ox-LDL levels were significantly correlated with TG levels(r=0.119,p<0.05)and TG/HDL ratio(r=0.390,p<0.01).Conclusions:It is concluded that ox-LDL levels were not associated with different LDL-C level categories from<55 mg/dL to>100 mg/dL in patients with T2D.However,the revealed association of ox-LDL with TG level and TG/HDL ratio may be considered in the clinic.

糖尿病患者血浆氧化、丙二醛修饰低密度脂蛋白及其自身抗体水平

目的探讨血浆氧化及丙二醛(MDA)修饰低密度脂蛋白(LDL)及其自身抗体与糖尿病(DM)及其他血脂项目之间的关系。方法选择DM患者、正常对照组各60例。采用酶联免疫吸附试验(ELISA)分别测定铜离子氧化型LDL(ox-LDL)、MDA修饰型LDL(MDA-LDL)及其自身抗体,同时对受检者血脂水平进行检测。结果DM患者血浆ox-LDL、MDA-LDL及其自身抗体水平均明显高于对照组(P<0.01),分别与总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)呈高度正相关,而与高密度脂蛋白胆固醇(HDL-C)呈负相关;且ox-LDL、MDA-LDL分别同其自身抗体呈高度正相关。结论DM患者ox-LDL、MDA-LDL及其自身抗体水平显著升高,可能参与动脉粥样硬化的发生、发展过程。

人血清氧化低密度脂蛋白自身抗体的提取和初步鉴定

目的提取和鉴定人血清氧化低密度脂蛋白(Ox-LDL)自身抗体。方法采用溴化氰活化的Sepharose4B交联Ox-LDL制备免疫吸附层析柱,从正常人血清中提取抗Ox-LDL自身抗体,采用ELISA法鉴定其免疫反应性,散射免疫比浊法分析自身抗体种类。结果用NaHCO3、醋酸盐和KCNS溶液洗脱,分别收集洗脱峰。8份正常人血清中均收集到Ox-LDL自身抗体,与Ox-LDL均具有良好的反应性。自身抗体种类中以IgG为主,其次为IgM。结论此法提取的抗Ox-LDL自身抗体同Ox-LDL具有良好的反应能力。

急性冠状动脉综合征患者血清抗apoA-1IgGs与oxLDL的相关性研究

目的研究急性冠状动脉综合征患者血清抗载脂蛋白A-l抗体的阳性率、血清oxLDL的水平和PON-1的活性,并探讨它们之间的相关性。方法选取68例急性冠状动脉综合征患者,以健康中老年人体检者70例为对照组,分别采用酶联免疫吸附法(ELISA)检测抗apoA-1IgGs的阳性率和血清oxLDL的水平,紫外分光光度法测定PON-1的活性。结果急性冠状动脉综合征组患者体内的apoA-1IgG和oxLDL水平比对照组明显升高(P<0.001),急性冠状动脉综合征组患者的抗apoA-1 IgGs阳性率为14.7%,阳性患者血清抗apoA-1IgG的滴度与其oxLDL水平存在正相关(r=0.469,P<0.05),而血清PON-1的活性差异无统计学意义。结论自身抗体抗apoA-1IgGs可能参与冠状动脉粥样硬化反应的发生与发展;急性冠状动脉综合征患者升高的oxLDL水平可能与抗apoA-1IgGs有关。

冠心病患者氧化低密度脂蛋白自身抗体的变化

目的探讨血清氧化低密度脂蛋白自身抗体(Ab-ox-LDL)与冠心病患者病变稳定性及病变程度的关系。方法根据临床诊断标准和冠状动脉造影结果,将60例患者分为非冠心病(CON)组、不稳定型心绞痛(UAP)组和稳定型心绞痛(SAP)组,采用ELISA法测定血清Ab-ox-LDL浓度。结果UAP组血清Ab-ox-LDL水平明显高于SAP和CON组(P<0.05),SAP组高于CON组(P<0.05);Ab-ox-LDL在UAP组和SAP组呈高度正相关(P<0.05)。结论血清Ab-ox-LDL与冠心病患者病变的严重程度和冠心病斑块的稳定性密切相关,在冠状动脉硬化进程中可能起着重要的作用。