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 Inform...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.展开更多
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
Six additives,i.e.,limestone,lime,magnesite,magnesia,dolomite and light-burned-dolomite,were added for investigating their influences on the pellet quality.For green balls,adding lime and light-burned-dolomite makes t...Six additives,i.e.,limestone,lime,magnesite,magnesia,dolomite and light-burned-dolomite,were added for investigating their influences on the pellet quality.For green balls,adding lime and light-burned-dolomite makes the wet drop strength decrease firstly,and then increase with further increase of additive dosage.Ca(OH)2 affects the bentonite properties at the beginning,but the binding property of Ca(OH)2 will be main when the dosage is higher.The other four additives decrease the drop strength for their disadvantageous physical properties.For preheated pellets,no mater what kind of additive is added,the compressive strength will be decreased because of unmineralized additives.For roasted pellets,calcium additives can form binding phase of calcium-ferrite,and suitable liquid phase will improve recrystallization of hematite,but excessive liquid will destroy the structure of pellets,so the compressive strength of pellet increases firstly and then drops.When adding magnesium additives,the strength will be decreased because of the oxidation of magnetite retarded by MgO.展开更多
Background Scavenger receptor that binds phosphatidylserine and oxidized lipoprotein/CXC chemokine ligand 16 （SR-PSOX/CXCL16） promotes foam cell formation through the tumor necrosis factor （TNF）-α mediated mechan...Background Scavenger receptor that binds phosphatidylserine and oxidized lipoprotein/CXC chemokine ligand 16 （SR-PSOX/CXCL16） promotes foam cell formation through the tumor necrosis factor （TNF）-α mediated mechanism. Because chemokine CXCL16 could be expressed in atherosclerotic lesions and induce smooth muscle cell （SMC） proliferation, we＇presume that the monocyte SR-PSOX/CXCL16 detection in the patients＇ peripheral blood will be important for early diagnosis and prognosis of atherosclerosis （AS）. Methods Enrolled in this study were 40 patients with acute coronary syndrome （ACS）, including 20 patients with acute myocardial infarction （AMI） and 20 patients with unstable angina pectoris （UAP）, and 20 normal controls. Monocytes in the peripheral blood were isolated, and the changes of expression of CXCL16/SR-PSOX mRNA were compared using reverse transcription-polymerase chain reaction （RT-PCR）, with β-actin as internal control. We compared the expression of CXCL16/SR-PSOX in the ACS subgroups, using Western-blot to analyze protein expression levels. Tissue sections were made from biopsy specimens taken from patients with infective endocarditis, liver cirrhosis, and lung cancer as well as normal controls. And the expression of CXCL16/SR- PSOX was analyzed with a confocal microscope. Results The expression of CXCL16/SR-PSOX mRNA and protein in the monocytes of peripheral blood was significantly higher in ACS patients than in normal controls （P〈0.05）; however, there was no significant difference in CXCL16/SR-PSOX expression between UAP group and AMI group （P〉0.05）. Immunofluorescence showed that there were low expression of SR-PSOX in normal vascular endothelial cells and enhanced expression in every layer of the infected vessels, while spreading from endothelial cells to surrounding tissues as infection worsens. Confocal microscopy showed that the expression of SR-PSOX was enhanced in the infiltrated lymphocytes in liver cirrhosis, and that the expression level was pr展开更多
Background To determine the binding activity of nuclear factor-KB (NF-KB) and the transcription of transforming growth factor-pi (TGF-β1) induced by oxidized low density lipoprotein (Ox-LDL) in rat mesangial cells an...Background To determine the binding activity of nuclear factor-KB (NF-KB) and the transcription of transforming growth factor-pi (TGF-β1) induced by oxidized low density lipoprotein (Ox-LDL) in rat mesangial cells and to elucidate the mechanism of renal injury of Ox-LDL.Methods NF-KB binding activity was measured by gel shift assay in mesangial cells with or without inducement of Ox-LDL. Protein kinase inhibitors and activtors were then used to determine the signal transduction pathways. In this course IKB protein expression was analyzed by Westerm blot assay. TGF-β1 mRNA was measured in mesangial cells exposed to Ox-LDL by RT-PCR assay. TGF-β1 promoter from -1551 to +57 were constructed into a pGL3-Basic vector with a luciferase reporting gene. A putative binding site of NF-KB was mutated. The wild and mutant promoters activity was analyzed by transfection into mesangial cells.Results NF-KB was activated by Ox-LDL persistently and rebounded in the early period. Ox-LDL induced NF-KB activation in a dose dependent way. It also induced IKB degradation in 2 hours and resumed to normal levels. NF-KB activation was not alleviated by inhibitors of protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and p38 MAP kinase (p38MAPK). Inhibitors of protein kinase C (PKC) and proteinsome inhibited the enhancement of NF-KB binding activity. Ox-LDL induced the transcription of TGF-β1 in a time and dose dependent manner. Mutation of the putative binding site of NF-KB reduced the activity of TGF-β1 promoter.Conclusion Ox-LDL induced activation of NF-KB persistently. It was probably regulated by the degradation of IkB mediated by PKC pathway. NF-KB may be involved in the enhancement of TGF-β1 induced by Ox-LDL in rat mesangial cells.展开更多
Background Studies have shown that oxidized low density lipoprotein （ox-LDL） promotes the pathogenesis and development of atherosclerosis （AS）, and that the proliferation, migration and phenotype alteration of vas...Background Studies have shown that oxidized low density lipoprotein （ox-LDL） promotes the pathogenesis and development of atherosclerosis （AS）, and that the proliferation, migration and phenotype alteration of vascular smooth muscle cells （vSMCs） into foam cells are critical changes in AS. It is proposed that ox-LDL might play a novel role in the pathologic process of vSMCs. The present study was performed ex vivo to investigate the effects of ox-LDL on the growth of cultured human vSMCs.Methods Using NaBr density gradient centrifugation, LDL from human plasma was isolated and purified. ox-LDL was produced from LDL after being incubated with CuSO4. ox-LDL was then added to the culture medium at different concentrations （25μg/ml, 50μg/ml, 75 μg/ml, 100μg/ml, 125μg/ml, and 150μg/ ml） for 7 days. The influence of ox-LDL on vSMC growth was observed from several aspects as growth curve, mitosis index, lipid staining, and in situ determination of apoptosis. The digital results were analyzed with SPSS 10.0.Results The ox-LDL produced ex vivo 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 25 μg,/ml demonstrated the strongest proliferation. At the concentration of 125 μg,/ml, ox-LDL suppressed the growth of vSMCs. At concentrations of 25 μg/ml and 50 μg/ml, ox-LDL presented powerful mitotic trigger. When the concentration of ox-LDL increased, the mitotic index of vSMCs decreased gradually, ox-LDL induced more foam cells from vSMCs with rich intracellular lipid accumulation at concentrations of 25μg/ml and 50μg/ml, ox-LDL at higher concentrations induced more apoptotic vSMCs.Conclusions ox-LDL at lower concentrations may trigger proliferation and phenotype alteration into foam cells of vSMCs, and at higher concentrations it may induce apoptosis in vSMCs, ox-LDL plays an important role in the pathogenesis and development of atherosclerosis by its effect on vSMCs proliferation, phenotype alteration a展开更多
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 t...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 gr展开更多
OBJECTIVE： To observe the influence of moxibustion temperature on blood lipids, endothelin-1（ET-1）, nitric oxide（NO）, and ET-1/NO in hyperlipidemia patients. METHODS： Forty-two primary hyperlipidemia patients we...OBJECTIVE： To observe the influence of moxibustion temperature on blood lipids, endothelin-1（ET-1）, nitric oxide（NO）, and ET-1/NO in hyperlipidemia patients. METHODS： Forty-two primary hyperlipidemia patients were randomly divided into two groups of 21 and treated with moxibustion at different temperatures. Moxibustion was performed with the moxa roll 2.5-3.0 cm from the skin in the treatment group and 4 cm in the control group, 10 min per point, once every other day. Skin temperature was precisely measured with a thermometer during moxibustion. After a 12-week treatment, seven measurements of blood lipids, ET-1, and NO were recorded. RESULTS： Total cholesterol and triglyceride, were lower in the treatment group than in the control group（P0.05）. Serum ET-1 and ET-1/NO was obvi-ously lowered in the treatment group（P0.001）. Moxibustion regulated NO and ET-1/NO in the treatment group much better than in the control group. CONCLUSION： Moxibustion can regulate blood lipids and clear blood vessels. Moxibustion at 45℃has a better effect than moxibustion at 38℃ on regulating blood lipids and protecting vascular endothelial function, indicating that suitable temperature influences the curative effect of moxibustion.展开更多
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
Objective： To investigate the effects of drug-containing serum of Chinese herbal compound, Xiongshao Capsule （芎芍胶囊, XS, for activating-blood） and Huanglian Capsule （黄连胶囊, HL, for dispellingtoxin） on the o...Objective： To investigate the effects of drug-containing serum of Chinese herbal compound, Xiongshao Capsule （芎芍胶囊, XS, for activating-blood） and Huanglian Capsule （黄连胶囊, HL, for dispellingtoxin） on the oxidized low-density lipoprotein （ox-LDL）-induced inflammatory factors in human umbilical vein endothelial cells （HUVECs）. Methods： Thirty-two rats were randomly divided into four groups： the blank control group treated with distilled water, the positive control group treated with simvastatin （1.8 mg/kg）, the test group I treated with Chinese herbal compound of XS （0.135 g/kg）, and the test group 1T treated with Chinese herbal compound of XS （0.135 g/kg） and HL （0.135 g/kg）. All the treatments were administered for 7 successive days by gastrogavage. Rats＇ blood serum was harvested 1 h after the last administration to prepare respective drug- containing serum. HUVECs were exposed to ox-LDL （100 μg/mL） to induce cell injury model and incubated with corresponding drug-containing serum for 24 h. Untreated HUVECs were set for blank control. Levels of interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, and soluble intercellular adhesion molecule-1 （slCAM-1） in supematant of cultured HUVECs were determined by enzyme-linked immunosorbent assay （ELISA）. HUVEC surface expressions of ICAM-1 and E-selectin were determined by flow cytometry. Results： Levels of IL-6, TNF-α, and sICAM-1 in the supernatant of HUVECs as well as the cell surface expressions of ICAM-1 and E-selectin significantly increased after 24-h ox-LDL stimulation （P〈0.01）, while the abnormal elevations, except slCAM-1 in the test group Ⅰ, were all reduced in the treated groups （the positive control and the two test groups） significantly （P〈0.01 or P〈0.05）. Besides, the effect in the test group Ⅱ seemed somewhat higher than that in the test group Ⅰ but with no statistical significance （P〉0.05）. Conclusion： Drug-containing serum of XS plus HL has展开更多
文摘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.
基金State Key Clinical Specialty Construction Project,China
文摘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.
基金Project(2008BAB32B06) supported by the Key Projects in the National Science and Technology Pillar Program during the 11th Five-year Plan PeriodProject(2009ybfz20) supported by the Program for Excellent Doctor’s Degree Paper in Central South University,ChinaProject(1343/74333001114) supported by the Postgraduate’s Paper Innovation Fund of Hunan Province,China
文摘Six additives,i.e.,limestone,lime,magnesite,magnesia,dolomite and light-burned-dolomite,were added for investigating their influences on the pellet quality.For green balls,adding lime and light-burned-dolomite makes the wet drop strength decrease firstly,and then increase with further increase of additive dosage.Ca(OH)2 affects the bentonite properties at the beginning,but the binding property of Ca(OH)2 will be main when the dosage is higher.The other four additives decrease the drop strength for their disadvantageous physical properties.For preheated pellets,no mater what kind of additive is added,the compressive strength will be decreased because of unmineralized additives.For roasted pellets,calcium additives can form binding phase of calcium-ferrite,and suitable liquid phase will improve recrystallization of hematite,but excessive liquid will destroy the structure of pellets,so the compressive strength of pellet increases firstly and then drops.When adding magnesium additives,the strength will be decreased because of the oxidation of magnetite retarded by MgO.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30400265 and 30671047）, Ministry of Education Science and Technology Key Project （No. 207078） and the Youth Foundation of Hunan Province Education Department （No. 06B079）.
文摘Background Scavenger receptor that binds phosphatidylserine and oxidized lipoprotein/CXC chemokine ligand 16 （SR-PSOX/CXCL16） promotes foam cell formation through the tumor necrosis factor （TNF）-α mediated mechanism. Because chemokine CXCL16 could be expressed in atherosclerotic lesions and induce smooth muscle cell （SMC） proliferation, we＇presume that the monocyte SR-PSOX/CXCL16 detection in the patients＇ peripheral blood will be important for early diagnosis and prognosis of atherosclerosis （AS）. Methods Enrolled in this study were 40 patients with acute coronary syndrome （ACS）, including 20 patients with acute myocardial infarction （AMI） and 20 patients with unstable angina pectoris （UAP）, and 20 normal controls. Monocytes in the peripheral blood were isolated, and the changes of expression of CXCL16/SR-PSOX mRNA were compared using reverse transcription-polymerase chain reaction （RT-PCR）, with β-actin as internal control. We compared the expression of CXCL16/SR-PSOX in the ACS subgroups, using Western-blot to analyze protein expression levels. Tissue sections were made from biopsy specimens taken from patients with infective endocarditis, liver cirrhosis, and lung cancer as well as normal controls. And the expression of CXCL16/SR- PSOX was analyzed with a confocal microscope. Results The expression of CXCL16/SR-PSOX mRNA and protein in the monocytes of peripheral blood was significantly higher in ACS patients than in normal controls （P〈0.05）; however, there was no significant difference in CXCL16/SR-PSOX expression between UAP group and AMI group （P〉0.05）. Immunofluorescence showed that there were low expression of SR-PSOX in normal vascular endothelial cells and enhanced expression in every layer of the infected vessels, while spreading from endothelial cells to surrounding tissues as infection worsens. Confocal microscopy showed that the expression of SR-PSOX was enhanced in the infiltrated lymphocytes in liver cirrhosis, and that the expression level was pr
文摘Background To determine the binding activity of nuclear factor-KB (NF-KB) and the transcription of transforming growth factor-pi (TGF-β1) induced by oxidized low density lipoprotein (Ox-LDL) in rat mesangial cells and to elucidate the mechanism of renal injury of Ox-LDL.Methods NF-KB binding activity was measured by gel shift assay in mesangial cells with or without inducement of Ox-LDL. Protein kinase inhibitors and activtors were then used to determine the signal transduction pathways. In this course IKB protein expression was analyzed by Westerm blot assay. TGF-β1 mRNA was measured in mesangial cells exposed to Ox-LDL by RT-PCR assay. TGF-β1 promoter from -1551 to +57 were constructed into a pGL3-Basic vector with a luciferase reporting gene. A putative binding site of NF-KB was mutated. The wild and mutant promoters activity was analyzed by transfection into mesangial cells.Results NF-KB was activated by Ox-LDL persistently and rebounded in the early period. Ox-LDL induced NF-KB activation in a dose dependent way. It also induced IKB degradation in 2 hours and resumed to normal levels. NF-KB activation was not alleviated by inhibitors of protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and p38 MAP kinase (p38MAPK). Inhibitors of protein kinase C (PKC) and proteinsome inhibited the enhancement of NF-KB binding activity. Ox-LDL induced the transcription of TGF-β1 in a time and dose dependent manner. Mutation of the putative binding site of NF-KB reduced the activity of TGF-β1 promoter.Conclusion Ox-LDL induced activation of NF-KB persistently. It was probably regulated by the degradation of IkB mediated by PKC pathway. NF-KB may be involved in the enhancement of TGF-β1 induced by Ox-LDL in rat mesangial cells.
文摘Background Studies have shown that oxidized low density lipoprotein （ox-LDL） promotes the pathogenesis and development of atherosclerosis （AS）, and that the proliferation, migration and phenotype alteration of vascular smooth muscle cells （vSMCs） into foam cells are critical changes in AS. It is proposed that ox-LDL might play a novel role in the pathologic process of vSMCs. The present study was performed ex vivo to investigate the effects of ox-LDL on the growth of cultured human vSMCs.Methods Using NaBr density gradient centrifugation, LDL from human plasma was isolated and purified. ox-LDL was produced from LDL after being incubated with CuSO4. ox-LDL was then added to the culture medium at different concentrations （25μg/ml, 50μg/ml, 75 μg/ml, 100μg/ml, 125μg/ml, and 150μg/ ml） for 7 days. The influence of ox-LDL on vSMC growth was observed from several aspects as growth curve, mitosis index, lipid staining, and in situ determination of apoptosis. The digital results were analyzed with SPSS 10.0.Results The ox-LDL produced ex vivo 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 25 μg,/ml demonstrated the strongest proliferation. At the concentration of 125 μg,/ml, ox-LDL suppressed the growth of vSMCs. At concentrations of 25 μg/ml and 50 μg/ml, ox-LDL presented powerful mitotic trigger. When the concentration of ox-LDL increased, the mitotic index of vSMCs decreased gradually, ox-LDL induced more foam cells from vSMCs with rich intracellular lipid accumulation at concentrations of 25μg/ml and 50μg/ml, ox-LDL at higher concentrations induced more apoptotic vSMCs.Conclusions ox-LDL at lower concentrations may trigger proliferation and phenotype alteration into foam cells of vSMCs, and at higher concentrations it may induce apoptosis in vSMCs, ox-LDL plays an important role in the pathogenesis and development of atherosclerosis by its effect on vSMCs proliferation, phenotype alteration a
文摘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 gr
文摘OBJECTIVE： To observe the influence of moxibustion temperature on blood lipids, endothelin-1（ET-1）, nitric oxide（NO）, and ET-1/NO in hyperlipidemia patients. METHODS： Forty-two primary hyperlipidemia patients were randomly divided into two groups of 21 and treated with moxibustion at different temperatures. Moxibustion was performed with the moxa roll 2.5-3.0 cm from the skin in the treatment group and 4 cm in the control group, 10 min per point, once every other day. Skin temperature was precisely measured with a thermometer during moxibustion. After a 12-week treatment, seven measurements of blood lipids, ET-1, and NO were recorded. RESULTS： Total cholesterol and triglyceride, were lower in the treatment group than in the control group（P0.05）. Serum ET-1 and ET-1/NO was obvi-ously lowered in the treatment group（P0.001）. Moxibustion regulated NO and ET-1/NO in the treatment group much better than in the control group. CONCLUSION： Moxibustion can regulate blood lipids and clear blood vessels. Moxibustion at 45℃has a better effect than moxibustion at 38℃ on regulating blood lipids and protecting vascular endothelial function, indicating that suitable temperature influences the curative effect of moxibustion.
文摘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）.
基金Supported by the National Developing Plan for Basic Key Items (973 Plan,No.2006CB504803)
文摘Objective： To investigate the effects of drug-containing serum of Chinese herbal compound, Xiongshao Capsule （芎芍胶囊, XS, for activating-blood） and Huanglian Capsule （黄连胶囊, HL, for dispellingtoxin） on the oxidized low-density lipoprotein （ox-LDL）-induced inflammatory factors in human umbilical vein endothelial cells （HUVECs）. Methods： Thirty-two rats were randomly divided into four groups： the blank control group treated with distilled water, the positive control group treated with simvastatin （1.8 mg/kg）, the test group I treated with Chinese herbal compound of XS （0.135 g/kg）, and the test group 1T treated with Chinese herbal compound of XS （0.135 g/kg） and HL （0.135 g/kg）. All the treatments were administered for 7 successive days by gastrogavage. Rats＇ blood serum was harvested 1 h after the last administration to prepare respective drug- containing serum. HUVECs were exposed to ox-LDL （100 μg/mL） to induce cell injury model and incubated with corresponding drug-containing serum for 24 h. Untreated HUVECs were set for blank control. Levels of interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, and soluble intercellular adhesion molecule-1 （slCAM-1） in supematant of cultured HUVECs were determined by enzyme-linked immunosorbent assay （ELISA）. HUVEC surface expressions of ICAM-1 and E-selectin were determined by flow cytometry. Results： Levels of IL-6, TNF-α, and sICAM-1 in the supernatant of HUVECs as well as the cell surface expressions of ICAM-1 and E-selectin significantly increased after 24-h ox-LDL stimulation （P〈0.01）, while the abnormal elevations, except slCAM-1 in the test group Ⅰ, were all reduced in the treated groups （the positive control and the two test groups） significantly （P〈0.01 or P〈0.05）. Besides, the effect in the test group Ⅱ seemed somewhat higher than that in the test group Ⅰ but with no statistical significance （P〉0.05）. Conclusion： Drug-containing serum of XS plus HL has
