Objective： Dyslipidemia is a leading cause of cardiovascular disease. At present, studies have shown that theincidence of cardiovascular disease in our country increased year by year. According to WHO statistics in 2...Objective： Dyslipidemia is a leading cause of cardiovascular disease. At present, studies have shown that theincidence of cardiovascular disease in our country increased year by year. According to WHO statistics in 2013, itshowed that about 17 million people worldwide die from coronary heart disease （CHD） every year. Currently, CHDis the first cause of death in western countries and the incidence of CHD also showed a trend of increasing. Inrecent years more experts and scholars at home and abroad found gene polymorphism is closely related tohigh-density lipoprotein cholesterol （HDLC） gene and triglyceride （TG） levels. Apolipoprotein （APO） gene is akind of popular polymorphic proteins, whose genetic polymorphisms is through the impact of lipid metabolism,and then closely related to cerebrovascular diseases. But the results are different in different populations and races,or even the opposite. Methods： This review will summarize the gene polymorphism loci of commonapolipoprotein-ApoA1, ApoA5, Apo B, ApoC3, ApoE, which is associated with lipid levels and cardiovasculardisease. Conclusion： It is important for us to get a further understand and prevent the occurrence and developmentof cardiovascular disease from gene level..展开更多
Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized...Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized protocol using 50:50 NiPAM:BAM copolymer nanoparticles with thermo-responsive properties as an affinity resin. Repeated pelleting and washing of nanoparticle-captured apoA-I is achieved through temperature cycling. The protein is then eluted using urea followed by an ion exchange step for protein concentration and depletion of nanoparticles.展开更多
Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that A...Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.展开更多
In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma H...In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I（and to a lesser extent with apoE and apoA-IV） and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.展开更多
Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surfa...Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ecto-F1-ATPase. Particularly, the role of the F1-ATPase pathway(s) in HDL-cholesterol uptake and apoA-Imediated endothelial protection suggests its potential importance in reverse cholesterol transport and its regulation might represent a potential therapeutic target for HDL-related therapy for cardiovascular diseases. Therefore, it is timely for us to better understand how this ecto-enzyme and downstream pathways are regulated and to develop pharmacologic interventions.展开更多
Thirty-six cases with hyperglycemia were treated with the method of promoting blood circulation and removing stasis in a course of 4 weeks. The treatment was significantly effective in correcting the abnormal viscosit...Thirty-six cases with hyperglycemia were treated with the method of promoting blood circulation and removing stasis in a course of 4 weeks. The treatment was significantly effective in correcting the abnormal viscosity of the blood by reducing the contents of total plasmic cholesterol (TC), triglyceride (TG) and apoprotein B (apoB), while the level of the apoprotein A (apoA) was elevated.展开更多
Is physical fatigue one of the major causes of motor vehicle accidents？ Our study results challenged this traditional belief, and indicated that motor vehicle induced whole body vibration （WBV） is the actual cause....Is physical fatigue one of the major causes of motor vehicle accidents？ Our study results challenged this traditional belief, and indicated that motor vehicle induced whole body vibration （WBV） is the actual cause. In this study, rats were subjected to simulated WBV. After 2 weeks all rats were evaluated by multiple physiological tests. Results indicated that WBV for short periods impaired the animal＇s mental judgment capabilities as well as sensory and motor functions. The primary reason for this is that WBV caused vasoconstriction, which decreased the cerebral blood flow as shown by Doppler imaging. This reduction in blood flow impaired the animal＇s ability to run a maze. Nerve functions were affected as well. This was shown by a reduction in nerve conduction velocity （NCV）. An increase in tail flick and Von Frey withdrawal times showed sensory deficits. Grip strength was also reduced. 4F （human apolipoprotein A-I molecule mimetic） conditioning has shown preventive effects against WBV injury as indicated by the above functional tests. This animal model simulated the most common motor vehicle travel vibration and validated the biological cause and mechanism of physiological impairment from WBV, which can be translated into a practical application for motor vehicle accident prevention.展开更多
文摘Objective： Dyslipidemia is a leading cause of cardiovascular disease. At present, studies have shown that theincidence of cardiovascular disease in our country increased year by year. According to WHO statistics in 2013, itshowed that about 17 million people worldwide die from coronary heart disease （CHD） every year. Currently, CHDis the first cause of death in western countries and the incidence of CHD also showed a trend of increasing. Inrecent years more experts and scholars at home and abroad found gene polymorphism is closely related tohigh-density lipoprotein cholesterol （HDLC） gene and triglyceride （TG） levels. Apolipoprotein （APO） gene is akind of popular polymorphic proteins, whose genetic polymorphisms is through the impact of lipid metabolism,and then closely related to cerebrovascular diseases. But the results are different in different populations and races,or even the opposite. Methods： This review will summarize the gene polymorphism loci of commonapolipoprotein-ApoA1, ApoA5, Apo B, ApoC3, ApoE, which is associated with lipid levels and cardiovasculardisease. Conclusion： It is important for us to get a further understand and prevent the occurrence and developmentof cardiovascular disease from gene level..
基金This work was funded by an Irish Research Council for Science,Engineering and Technology Postdoctoral Fellowship(M.L.)the Marianne and Marcus Wallenberg Foundation(M.L.)+2 种基金the EU FP6 project NanoInteract(NMP4-CT-2006-033231)and the SFI SRC BioNanoInteract(07 SRC B1155)Centre for Nano-Vaccine,Copenhagen,Denmark,and the Swedish Research Council(VR).
文摘Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized protocol using 50:50 NiPAM:BAM copolymer nanoparticles with thermo-responsive properties as an affinity resin. Repeated pelleting and washing of nanoparticle-captured apoA-I is achieved through temperature cycling. The protein is then eluted using urea followed by an ion exchange step for protein concentration and depletion of nanoparticles.
文摘目的:探讨载脂蛋白C1(apolipoprotein C1,APOC1)基因多态性与缺血性中风易感性及临床指标的相关性。方法:选择广西中医药大学第一附属医院脑病二科533例缺血性脑卒中患者为病例组,并选择同时期该院体检中心健康体检者或骨科及其他病势较轻的外伤患者531例为对照组。应用Sequenom技术对APOC1基因rs4420638位点进行基因分型。应用PLINK软件进行遗传关联分析。结果:两组受试者rs4420683的基因型频率比较,差异具有统计学意义(χ^(2)=8.725 P=0.013);在显性模型、隐形模型、加性模型中,APOC1基因rs4420683多态性与缺血性中风痰瘀证发生风险的关联比较,差异无统计学意义(P>0.05);经年龄、性别校正后,关联仍无统计学意义(P_(adj)>0.05);按性别分层分析,在男性、女性受试者中,APOC1基因的多态性与缺血性中风痰瘀证发生风险的关联均无统计学意义(P>0.05);校正年龄后,关联仍无统计学意义(P_(adj)>0.05)。在校正性别、年龄后结果显示,APOC1基因多态性与缺血性中风痰瘀证患者收缩压、舒张压水平的相关性比较,差异均无统计学意义(P_(adj)>0.05);APOC1基因rs4420683多态性与缺血性中风痰瘀证患者空腹血糖及餐后2 h血糖的相关性比较,差异均无统计学意义(P_(adj)>0.05);APOC1基因多态性与缺血性中风痰瘀证患者的高密度脂蛋白(high density lipoprotein,HDL)[显性模型:β=0.09,95%CI(0.02,0.16),P=0.010)]、低密度脂蛋白(low density lipoprotein,LDL)[显性模型:β=0.25,95%CI(0.03,0.46),P=0.025)]显著相关;rs4420683多态性与缺血性中风痰瘀证患者HDL[显性模型:β_(adj)=0.08,95%CI adj(0.01,0.15),P_(adj)=0.021]、LDL[显性模型:β_(adj)=0.23,95%CI adj(0.01,0.44),P_(adj)=0.037]也具有相关性。结论:APOC1基因rs4420638的多态性可能会对缺血性中风痰瘀证的发生和发展产生影响,其作用机制可能涉及对血脂代谢的调节。
基金supported in part by the National Natural Science Foundation of China,No.81160146
文摘Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.
基金supported by National Institute of Health Grant HL-48739 and HL-68216
文摘In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I（and to a lesser extent with apoE and apoA-IV） and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.
基金Supported by An INSERM Avenir Grant (Martinez LO)ANR (Martinez LO and Lichtenstein L, #GENO 102 01)+1 种基金the French Association pour la Recherche sur le Cancer (Vantourout P and Champagne E, #3711-3913-4847)An INSERM young scientist fellowship (Pons V)
文摘Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ecto-F1-ATPase. Particularly, the role of the F1-ATPase pathway(s) in HDL-cholesterol uptake and apoA-Imediated endothelial protection suggests its potential importance in reverse cholesterol transport and its regulation might represent a potential therapeutic target for HDL-related therapy for cardiovascular diseases. Therefore, it is timely for us to better understand how this ecto-enzyme and downstream pathways are regulated and to develop pharmacologic interventions.
文摘Thirty-six cases with hyperglycemia were treated with the method of promoting blood circulation and removing stasis in a course of 4 weeks. The treatment was significantly effective in correcting the abnormal viscosity of the blood by reducing the contents of total plasmic cholesterol (TC), triglyceride (TG) and apoprotein B (apoB), while the level of the apoprotein A (apoA) was elevated.
文摘Is physical fatigue one of the major causes of motor vehicle accidents？ Our study results challenged this traditional belief, and indicated that motor vehicle induced whole body vibration （WBV） is the actual cause. In this study, rats were subjected to simulated WBV. After 2 weeks all rats were evaluated by multiple physiological tests. Results indicated that WBV for short periods impaired the animal＇s mental judgment capabilities as well as sensory and motor functions. The primary reason for this is that WBV caused vasoconstriction, which decreased the cerebral blood flow as shown by Doppler imaging. This reduction in blood flow impaired the animal＇s ability to run a maze. Nerve functions were affected as well. This was shown by a reduction in nerve conduction velocity （NCV）. An increase in tail flick and Von Frey withdrawal times showed sensory deficits. Grip strength was also reduced. 4F （human apolipoprotein A-I molecule mimetic） conditioning has shown preventive effects against WBV injury as indicated by the above functional tests. This animal model simulated the most common motor vehicle travel vibration and validated the biological cause and mechanism of physiological impairment from WBV, which can be translated into a practical application for motor vehicle accident prevention.
