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Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke
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作者 Shuai Feng Juanji Li +6 位作者 Tingting Liu Shiqi Huang Xiangliang Chen Shen Liu Junshan Zhou Hongdong Zhao Ye Hong 《Neural Regeneration Research》 SCIE CAS 2025年第2期491-502,共12页
Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit... Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke. 展开更多
关键词 inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome POLaRIZaTION
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Low-density lipoprotein receptor-related protein 2(LRP2)is required for lipid export in the midgut of the migratory locust,Locusta migratoria
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作者 Yiyan Zhao Weimin Liu +6 位作者 Xiaoming Zhao Zhitao Yu Hongfang Guo Yang Yang Hans Merzendorfer Kun Yan Zhu Jianzhen Zhang 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第5期1618-1633,共16页
Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholestero... Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts. 展开更多
关键词 Locusta migratoria low-density lipoprotein receptor-related protein 2 MIDGUT lipids transport RNai
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Synthetic high-density lipoprotein(sHDL):a bioinspired nanotherapeutics for managing periapical bone inflammation
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作者 Renan Dal-Fabbro Minzhi Yu +3 位作者 Ling Mei Hajime Sasaki Anna Schwendeman Marco C.Bottino 《International Journal of Oral Science》 SCIE CAS CSCD 2024年第3期460-470,共11页
Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affectin... Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation. 展开更多
关键词 INFLaMMaTION lipoprotein markedly
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Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity
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作者 Jun-feng ZHANG Feng-qing CAI +1 位作者 Xiu-cai ZHANG Qing YE 《Current Medical Science》 SCIE CAS 2024年第4期692-697,共6页
Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various infla... Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various inflammation-related diseases.The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.Methods Based on hepatic ultrasound,a total of 504 children with obesity(357 with NAFLD and 147 without NAFLD)were included in the study.The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses.Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.Results The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD[0.52(0.44-0.67)versus 0.44(0.34-0.57),P<0.001].Multivariate stepwise logistic regression analysis demonstrated that the MHR[odds ratio(OR):1.033,95%confidence interval(CI):1.015-1.051;P<0.001]was an independent predictor of NAFLD in childhood obesity patients,as were age(OR:1.205,95%CI:1.059-1.371;P=0.005],waist circumference[OR:1.037,95%CI:1.008-1.067;P=0.012],and alanine transaminase[OR:1.067,95%CI:1.045-1.089;P<0.001].Additionally,MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.Conclusion The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity. 展开更多
关键词 nonalcoholic fatty liver disease OBESITY monocyte-to-high-density lipoprotein ratio MaRKER
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Initial decrease in the lipoprotein(a)level is a novel prognostic biomarker in patients with acute coronary syndrome
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作者 Yasuhiko Saeki Jun Sawaguchi +7 位作者 Satori Akita Taka-aki Takamura Kosuke Fujibayashi Minoru Wakasa Hironobu Akao Michihiko Kitayama Yasuyuki Kawai Kouji Kajinami 《World Journal of Cardiology》 2024年第6期329-338,共10页
BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)level... BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)levels are altered by various conditions during the acute phase of ACS,resulting in subsequent cardiovascular events.METHODS From September 2009 to May 2016,377 patients with ACS who underwent emergent coronary angiography,and 249 who completed≥1000 d of follow-up were enrolled.Lp(a)levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention(PCI)to 48 h after PCI.The primary endpoint was the occurrence of major adverse cardiac events(MACE;cardiac death,other vascular death,ACS,and non-cardiac vascular events).RESULTS The mean circulating Lp(a)level decreased significantly from pre-PCI(0 h)to 12 h after(19.0 mg/dL to 17.8 mg/dL,P<0.001),and then increased significantly up to 48 h after(19.3 mg/dL,P<0.001).The changes from 0 to 12 h[Lp(a)Δ0-12]significantly correlated with the basal levels of creatinine[Spearman’s rank correlation coefficient(SRCC):-0.181,P<0.01]and Lp(a)(SRCC:-0.306,P<0.05).Among the tertiles classified according to Lp(a)Δ0-12,MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups(66.2%vs 53.6%,P=0.034).A multivariate analysis revealed that Lp(a)Δ0-12[hazard ratio(HR):0.96,95%confidence interval(95%CI):0.92-0.99]and basal creatinine(HR:1.13,95%CI:1.05-1.22)were independent determinants of subsequent MACE.CONCLUSION Circulating Lp(a)levels in patients with ACS decreased significantly after emergent PCI,and a greater decrease was independently associated with a worse prognosis. 展开更多
关键词 lipoprotein(a) acute coronary syndrome Percutaneous coronary intervention Major adverse cardiac events PROGNOSIS
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Monocyte to high-density lipoprotein cholesterol ratio as a predictor of the activity of thyroid-associated ophthalmopathy
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作者 Xing-Hong Sun Xiao-Wen Zhang +5 位作者 Chen Han Xin Dou Xue-Ying He Meng-Ru Su Feng Jiang Song-Tao Yuan 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第12期2276-2281,共6页
AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified int... AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified into two groups based on clinical activity score(CAS)scoring criteria:high CAS group(n=62,the CAS score was≥3);low CAS group(n=25,the CAS score was<3).In addition,a group of healthy people(n=114)were included to compared the MHR.Proptosis,MHR,average signal intensity ratio(SIR),average lacrimal gland(LG)-SIR,average extraocular muscles(EOM)area from 87 patients with TAO were calculated in magnetic resonance imaging(MRI),and compared between these two groups.Correlation testing was utilized to evaluate the association of parameters among the clinical variables.RESULTS:Patients in high CAS group had a higher proptosis(P=0.041)and MHR(P=0.048).Compared to the healthy group,the MHR in the TAO group was higher(P=0.001).Correlation testing declared that CAS score was strongly associated with proptosis and average SIR,and MHR was positively associated with CAS score,average SIR,and average LG-SIR.The area under the receiver operating characteristic curve(AUC)of MHR was 0.6755.CONCLUSION:MHR,a novel inflammatory biomarker,has a significant association with CAS score and MRI imaging(average SIR and LG-SIR)and it can be a new promising predictor during the active phase of TAO. 展开更多
关键词 thyroid-associated ophthalmopathy monocyte to high-density lipoprotein cholesterol ratio disease activity
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Association between sensitivity to thyroid hormones and non-highdensity lipoprotein cholesterol levels in patients with type 2 diabetes mellitus
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作者 Xiao-Ye Duan Jun-Ling Fu +2 位作者 Li-Na Sun Zhi-Jing Mu Shuang-Ling Xiu 《World Journal of Diabetes》 SCIE 2024年第10期2081-2092,共12页
BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has... BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM. 展开更多
关键词 Non-high-density lipoprotein cholesterol Sensitivity to thyroid hormones Type 2 diabetes mellitus Thyroid feedback quantile-based index Free triiodothyronine/free thyroxine ratio
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Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment
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作者 Yi Wang Yuning Li +6 位作者 Yakun Gu Wei Ma Yuying Guan Mengyuan Guo Qianqian Shao Xunming Ji Jia Liu 《Neural Regeneration Research》 SCIE CAS 2025年第9期2598-2610,共13页
Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to... Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive impairment.We found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic stroke.In addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic stroke.Serum phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic stroke.Furthermore,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein levels.Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein levels.Taken together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment. 展开更多
关键词 BIOMaRKER high-density lipoprotein ischemic stroke phosphorylatedα-synuclein poststroke cognitive impairment
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Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance
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作者 Beibei Wu Yuqing Liu +4 位作者 Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng 《Neural Regeneration Research》 SCIE CAS 2025年第3期695-714,共20页
Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar... Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease. 展开更多
关键词 aBCa1 alzheimer's disease aMYLOID-BETa apolipoprotein E cholesterol metabolism LIVER liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid
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Correlation of Helicobacter pylori infection with high-density lipoprotein cholesterol levels and pulse wave conduction velocity
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作者 Yue-Xi Li Xiao-Qin Liu +1 位作者 Yu-Han Luo Qiao-Li Wang 《Clinical Research Communications》 2024年第4期33-38,共6页
Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's dise... Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's disease.However,the relationship between HP and lipid metabolism and atherosclerosis remains unclear.This study aims to investigate the association between H.pylori infection and high-density lipoprotein cholesterol levels and pulse wave conduction velocity.Methods:This is a report of a cross-sectional study that collected data from 2,827 participants.The data collected included results of life questionnaires,laboratory tests,13C-urea breath test(13C-UBT),and pulse wave conduction velocity test.Based on the results of the 13C-UBT test,the subjects were divided into two groups:the HP-uninfected group(HP−)and the HP-infected group(HP+).The study compared the differences in HDL-C levels and brachial-ankle pulse wave velocity(baPWV)between the two groups.One-way regression analysis was used to identify potential factors affecting HDL-C levels in the study population.Multiple regression equations were presented to analyze whether HP infection was an independent risk factor for abnormal HDL-C metabolism in the population.Results:Univariate analysis demonstrated that high-density lipoprotein cholesterol(HDL-C)levels were significantly lower in the HP+group compared to the HP−group,with a mean difference ofβ=−18.1 mg/dl(95%CI:−19.3 to−17.0,P<0.001).After adjusting for all variables,the HDL-C levels remained lower in the HP+group compared to the HP-group,with a mean difference ofβ=−17.4 mg/dl(95%CI:−18.2 to−16.7,P<0.001).These findings suggest that H.pylori infection is independently associated with abnormal HDL-C metabolism.Additionally,brachial-ankle pulse wave velocity(baPWV)was higher in the HP+group than in the HP−group on both sides.On the right side,the baPWV was 1,713.4±231.4 cm/s in the HP+group compared to 1,542.8±237.5 cm/s in the HP−group(t=−18.30,P<0.001).On the left side,the baPWV was 1,743.7±238.8 cm/s in the HP+group compared to 1,562.8±256.3 cm/s in the HP−group(t=−18.23,P<0.001).These results indicate a significant association between H.pylori infection and increased arterial stiffness,as measured by baPWV.Conclusion:Helicobacter pylori infection is associated with a decrease in high-density lipoprotein cholesterol levels and an increase in pulse wave conduction velocity. 展开更多
关键词 Helicobacter pylori CHOLESTEROL high-density lipoprotein aTHEROSCLEROSIS
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Genetic Screening of the Lipoprotein Lipase Gene for Mutations in Chinese Subjects with or without Hypertriglyceridemia 被引量:3
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作者 杨宇虹 穆云祥 +4 位作者 赵郁 刘新宇 赵莉莉 汪军梅 解用虹 《Journal of Genetics and Genomics》 SCIE CAS CSCD 北大核心 2007年第5期381-391,共11页
Objective: To investigate the association between the mutations in lipoprotein lipase gene and hypertriglyceridemia (HTG). Methods: The lipoprotein lipase (LPL) gene was screened for mutations in 386 Chinese sub... Objective: To investigate the association between the mutations in lipoprotein lipase gene and hypertriglyceridemia (HTG). Methods: The lipoprotein lipase (LPL) gene was screened for mutations in 386 Chinese subjects with (108 cases in the HTG group) or without HTG (278 cases in the control group), by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Results: One novel silent mutation L103L, one missense mutation P207L, three splicing mutations Int3/3' -ass/C(-6)→T, and the common S447X polymorphism has been identified in the whole coding region and exon-intron junctions of the LPL gene were examined. Heterozygous P207L found in the HTG group was the first case reported in Asia and subsequently another P207L heterozygote was found in the proband's family, all of which suggested that P207L was one of the causes of familial combined hyperlipidemia, but was not so prevalent as that in French Canadian. Int3/3'-ass/C(-6)→T was found in both groups in the present study although it was regarded as a pathogenic variant to HTG earlier on. Moreover about the beneficial polymorphism S447X, there was also some supportive evidence that the levels of triglycerides (TG) in S447X carriers were significantly lower than noncarders in the subjects without HTG. Conclusions: The association between the LPL variants and HTG is quite complicated and versatile, genotyping of LPL in a larger-scale screening should be necessary and justifiable. 展开更多
关键词 lipoprotein lipase MUTaTIONS CHINESE HYPERTRIGLYCERIDEMIa
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Lp-PLA2、hs-CRP和FIB联合检测在急性脑梗死诊断中的应用 被引量:3
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作者 孟凤琴 曹军 +2 位作者 石亚志 李战永 于奇 《标记免疫分析与临床》 CAS 2024年第2期287-291,共5页
目的探讨血浆脂蛋白相关磷脂酶A2(Lp-PLA2)、超敏C反应蛋白(hs-CRP)和纤维蛋白原(FIB)联合检测在急性脑梗死诊断中的临床价值。方法收集我院240例急性脑梗死的住院患者作为研究对象(脑梗组),以100例门诊体检健康人员为对照组,比较两组... 目的探讨血浆脂蛋白相关磷脂酶A2(Lp-PLA2)、超敏C反应蛋白(hs-CRP)和纤维蛋白原(FIB)联合检测在急性脑梗死诊断中的临床价值。方法收集我院240例急性脑梗死的住院患者作为研究对象(脑梗组),以100例门诊体检健康人员为对照组,比较两组人群的一般临床数据及检验结果,记录患者入院时的NIHSS评分。分析急性脑梗死患者血浆Lp-PLA2、hs-CRP和FIB水平与其神经功能缺损程度的关系,进行多因素Logistic回归分析确定急性脑梗死的危险因素,利用ROC曲线评估患者血浆Lp-PLA2、hs-CRP和FIB水平对急性脑梗死的诊断价值。结果重度脑梗死患者的Lp-PLA2、hs-CRP和FIB水平均高于轻度及中度脑梗死患者(P<0.05);与对照组比较,脑梗组患者的血浆Lp-PLA2、hs-CRP和FIB水平均显著升高,差异均具有统计学意义(P<0.05)。血浆Lp-PLA2、hs-CRP和FIB水平与急性脑梗死发病风险显著相关(P<0.05)。Lp-PLA2、hs-CRP和FIB 3个指标中,Lp-PLA2的ROC曲线下面积最大,诊断价值最高;Lp-PLA2、hs-CRP和FIB联合检测能显著提高急性脑梗死的诊断效率。结论联合检测Lp-PLA2、hs-CRP和FIB对判断ACI患者神经功能缺损程度具有较高价值。 展开更多
关键词 急性脑梗死 脂蛋白相关磷脂酶a2 超敏C反应蛋白 纤维蛋白原
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Lp-PLA2 LP(a)ApoB/ApoA-1水平与急性脑梗死严重程度及预后的相关性分析
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作者 薛涵 高静 +5 位作者 王冬静 赵雪 张艳利 刘莉 王利民 刘有为 《河北医学》 CAS 2024年第5期857-863,共7页
目的:探究脂蛋白相关磷脂酶A2(Lp-PLA2)、脂蛋白a[LP(a)]、载脂蛋白B(ApoB/)/载脂蛋白A-1(ApoA-1)的表达水平与急性脑梗死(ACI)的严重程度和预后的相关性。方法:选择我院2022年1月至2023年1月收治的ACI患者122例作为病例组,根据疾病严... 目的:探究脂蛋白相关磷脂酶A2(Lp-PLA2)、脂蛋白a[LP(a)]、载脂蛋白B(ApoB/)/载脂蛋白A-1(ApoA-1)的表达水平与急性脑梗死(ACI)的严重程度和预后的相关性。方法:选择我院2022年1月至2023年1月收治的ACI患者122例作为病例组,根据疾病严重程度分为轻度组(54例)、中度组(49例)、重度组(19例),另选择同期体检健康者作为对照组(97例)。根据预后效果分为预后良好组(88例)和预后不良组(34例)。比较病例组和对照组患者的基本资料和生化指标的差异性,分析Lp-PLA2、LP(a)、ApoB/ApoA-1的表达水平对患者病情严重程度和预后效果影响。结果:病例组患者年龄、吸烟史、高血压例数、收缩压、LDL-C、LP(a)、Lp-PLA2指标高于对照组(P<0.05),HDL-C指标低于对照组(P<0.05),多因素Logistic回归分析结果,年龄、吸烟史、高血压、收缩压、HDLC、LDLC、LPa、LpPLA2、ApoB/ApoA-1是影响ACI发生的独立危险因素(P<0.05)。重度组患者Lp-PLA2、LP(a)、ApoB/ApoA-1指标显著高于轻度组和中度组(P<0.05),中度组Lp-PLA2、LP(a)、ApoB/ApoA-1指标显著高于轻度组(P<0.05),Spearman相关性比较,Lp-PLA2、LP(a)、ApoB/ApoA-1指标与患者病情严重程度呈正相关(r=0.796、0.718、0.451,P<0.05)。预后良好组患者Lp-PLA2、LP(a)、ApoB/ApoA-1指标显著高于预后不良组(P<0.05),ROC曲线分析结果显示,联合预测AUC为0.987。结论:高龄、血压血脂异常、生活习惯较差者更易患ACI,而Lp-PLA2、ApoB/ApoA-1水平与ACI的严重程度和预后效果呈明显的相关性,通过检测可有效评估患者病情发展,具有较高临床价值。 展开更多
关键词 急性脑梗死 脂蛋白相关磷脂酶 脂蛋白a 载脂蛋白B/载脂蛋白a-1
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Lipoprotein(a) in type 2 diabetic subjects and its relationship to diabetic microvascular complications 被引量:13
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作者 Radhakrishnan Chandni Kollengode Parameswaran Ramamoorthy 《World Journal of Diabetes》 SCIE CAS 2012年第5期105-109,共5页
AIM: To estimate the level of serum lipoprotein (a) [Lp (a)] in type 2 diabetes mellitus patients and to determine the relationship between Lp(a) in type 2 diabetes mellitus patients and micro-vascular complications. ... AIM: To estimate the level of serum lipoprotein (a) [Lp (a)] in type 2 diabetes mellitus patients and to determine the relationship between Lp(a) in type 2 diabetes mellitus patients and micro-vascular complications. METHODS: A cross sectional study was performed that enrolled 144 subjects with type 2 diabetes mellitus above the age of 25 years attending outpatient clinic of Government Medical College, Kozhikode. Lp(a) levels were measured quantitatively in venous samples using Turbidimetric Immunoassay in all subjects. Each patient was evaluated for micro vascular complications, namely diabetic retinopathy, nephropathy and neuropathy. The relationship between Lp(a) levels and the micro vascular complications was assessed by univariate analysis. RESULTS: Mean age of cases was 53.93 ± 10.74 years with a male to female ratio of 1.3:1. Mean duration of diabetes was 9.53 ± 7.3 years. Abnormal Lp(a) levels (≥ 30 mg/dL) were observed in 38 (26.4%) diabetic subjects. Seventy-eight (54.16%) cases had diabetic nephropathy and significantly higher Lp(a) levels were found among these cases [Median 28.2 mg/dL (Interquartile range; IQR 24.4-33.5) vs 19.3 mg/dL (IQR 14.7-23.5); P < 0.05]. Retinopathy was present among 66 (45.13%) cases and peripheral neuropathy was detected among 54 (37.5%) cases. However, Lp(a) levels were not significantly different among those with or without retinopathy and neuropathy. Positive correlation was found between higher Lp(a) levels and duration of diabetes (r = 0.165, P < 0.05) but not with HbA1c values (r = - 0.083). CONCLUSION: Abnormal Lp(a) levels were found among 26.4% of diabetic subjects. Patients with diabetic nephropathy had higher Lp(a) levels. No association was found between Lp(a) levels and diabetic retinopathy or neuropathy. Longer duration of diabetes correlated with higher Lp(a) levels. 展开更多
关键词 Diabetes MELLITUS lipoprotein(a) Micro vascular complications DIaBETIC NEPHROPaTHY DIaBETIC RETINOPaTHY DIaBETIC NEUROPaTHY
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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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脂蛋白(a)与高龄慢性心力衰竭急性失代偿患者的预后相关性研究 被引量:1
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作者 冯超 杨雪圆 冯津萍 《中华老年心脑血管病杂志》 CAS 北大核心 2024年第3期254-257,共4页
目的 分析脂蛋白(a)[Lp(a)]与年龄≥80岁慢性心力衰竭(CHF)患者不良预后之间的关系,以及高龄CHF患者不良预后的影响因素。方法 收集2018年6月至2021年8月天津大学胸科医院心脏重症病房收治的高龄CHF急性失代偿患者135例,根据血清Lp(a)水... 目的 分析脂蛋白(a)[Lp(a)]与年龄≥80岁慢性心力衰竭(CHF)患者不良预后之间的关系,以及高龄CHF患者不良预后的影响因素。方法 收集2018年6月至2021年8月天津大学胸科医院心脏重症病房收治的高龄CHF急性失代偿患者135例,根据血清Lp(a)水平,分为高Lp(a)组[Lp(a)≥300 mg/L]73例和低Lp(a)组[Lp(a)<300 mg/L]62例,收集所有入组患者基线临床资料、12个月内随访结果,主要终点事件为因心力衰竭再住院和(或)全因死亡的复合终点。采用Kaplan-Meier生存曲线比较2组生存情况,采用logistic回归分析高龄CHF患者1年内发生终点事件的危险因素。结果 高Lp(a)组慢性肾脏病比例,同型半胱氨酸、TC及LDL-C水平高于低Lp(a)组,差异有统计学意义(P<0.05)。Kaplan-Meier生存分析显示,低Lp(a)组1年内无主要终点事件平均生存时间长于高Lp(a)组[9.8个月(95%CI:8.884~10.665)vs 8.2个月(95%CI:7.057~9.272),P<0.05]。多因素logistic回归分析显示,Lp(a)≥300 mg/L(OR=2.841,95%CI:1.133~7.092,P=0.026)、女性(OR=2.809,95%CI:1.111~7.092,P=0.029)、使用利尿剂(OR=4.631,95%CI:1.103~19.443,P=0.036)是患者1年内发生主要终点事件的独立危险因素。结论 Lp(a)≥300 mg/L是高龄CHF患者1年内发生因心力衰竭再住院和(或)全因死亡的独立危险因素。 展开更多
关键词 心力衰竭 脂蛋白(a) 预后 慢性心力衰竭急性失代偿
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High-density lipoprotein and atherosclerosis: Roles of lipid transporters 被引量:10
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作者 Yoshinari Uehara Keijiro Saku 《World Journal of Cardiology》 CAS 2014年第10期1049-1059,共11页
Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-... Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases. 展开更多
关键词 aTP-BINDING CaSSETTE transporter aTP-bind-ing CaSSETTE a1 aTP-BINDING CaSSETTE G1 apolipopro-tein a-I HIGH-DENSITY lipoprotein HIGH-DENSITY lipopro-tein therapy aPOa-I MIMETIC peptide Reconstitutedf HIGH-DENSITY lipoprotein
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Lipoprotein metabolism in nonalcoholic fatty liver disease 被引量:8
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作者 Zhenghui Gordon Jiang Simon C. Robson Zemin Yao 《The Journal of Biomedical Research》 CAS 2013年第1期1-13,共13页
Nonalcoholic fatty liver disease (NAFLD), an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to li... Nonalcoholic fatty liver disease (NAFLD), an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellu- lar role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metab- olism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD. 展开更多
关键词 nonalcoholic fatty liver disease (NaFLD) hepatic steatosis nonalcoholic steatohepatitis apolipo-protein lipoprotein metabolism very low density lipoprotein
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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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Association between Lipoprotein(a) Levels and Metabolic Syndrome in a Middle-aged and Elderly Chinese Cohort 被引量:5
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作者 WU Xue Yan LIN Lin +12 位作者 Qi Hong Yan DU Rui HU Chun Yan MA Li Na PENG Kui LI Mian XU Yu XU Min CHEN Yu Hong LU Jie Li BI Yu Fang WANG Wei Qing NING Guang 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2019年第7期477-485,共9页
Objective The association between lipoprotein(a)[Lp(a)] levels and metabolic syndrome(MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between L... Objective The association between lipoprotein(a)[Lp(a)] levels and metabolic syndrome(MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between Lp(a) levels and MetS in a middle-aged and elderly Chinese cohort. Methods A cross-sectional study of 10,336 Chinese adults aged 40 years or older was conducted in Jiading District, Shanghai, China. Logistic regression analysis was used to evaluate the association between serum Lp(a) levels and MetS. Results In the overall population, 37.5% of participants had MetS. Compared with individuals in the lowest quartile of serum Lp(a) levels, those in the highest quartile had a lower prevalence of MetS(30.9% vs. 46.9%, P for trend < 0.0001). Multivariate logistic regression analyses showed that compared with participants in the bottom quartile of serum Lp(a) levels, those in the top quartile had decreased odds ratio(OR) for prevalent MetS [multivariate-adjusted OR 0.45(95% confidence interval 0.39-0.51);P < 0.0001]. Additionally, Lp(a) level was conversely associated with the risk of central obesity, high fasting glucose, high triglycerides, and low HDL cholesterol, but not with hypertension. Stratified analyses suggested that increasing levels of Lp(a) was associated with decreased risk of MetS in all the subgroups. Conclusion Serum Lp(a) level was inversely associated with the risk of prevalent MetS in a middle-aged and elderly Chinese cohort. 展开更多
关键词 CaRDIOVaSCULaR risk factor lipoprotein(a) METaBOLIC syndrome
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