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
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
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
Background Alteration in the protein composition of high-density lipoprotein （HDL） has been proposed as a mechanism for the development of coronary heart disease （CHD）.In HDL,an increase in serum amyloid A protein...Background Alteration in the protein composition of high-density lipoprotein （HDL） has been proposed as a mechanism for the development of coronary heart disease （CHD）.In HDL,an increase in serum amyloid A protein （SAA） accompanying the decrease in apolipoprotein A-I （apoA-I） has been found during the acute inflammation period.However,whether this phenomenon persists in CHD patients,a disease related to inflammation,is unknown.The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients.Methods Overall,98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study.Potassium bromide （KBr） density gradient ultracentrifugation was used to isolate HDL from plasma.The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits.Pearson＇s correlation and general linear models were used in the analysis.Results Compared with controls,patients with CHD had a significant decrease in the amount of apoA-I （（14.21±8.44） μg/ml vs.（10.95±5.95） μg/ml,P =0.003） in HDL and a significant increase in the amount of log SAA （1.21±0.46 vs.1.51±0.55,P 〈0.00001）.Differences were independent of age,body mass index （BMI）,HDL cholesterol （HDL-C）,and other factors.An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group （β =2.0,P =0.026）.In the general linear model,changes in Iog（SAA）,age,age2,gender,BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I.Conclusions This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients,indicating the alteration of protein composition in HDL.However,the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.展开更多
METHODS： We determined the serum level of apolipoprotein A-I （APO A-I）, haptoglobin （HPT） and a-2 macroglobulin （A2I） with an automatic nephelometer in 63 children （age range 4-17 years, mean 10 years） with b...METHODS： We determined the serum level of apolipoprotein A-I （APO A-I）, haptoglobin （HPT） and a-2 macroglobulin （A2I） with an automatic nephelometer in 63 children （age range 4-17 years, mean 10 years） with biopsy-verified chronic HBeAg-positive hepatitis B. Fibrosis stage and inflammation grade were assessed in a blinded fashion according to Batts and Ludwig. We defined mild liver fibrosis as a score ≤2 and advanced fibrosis as a score equal to 3. ROC analysis was used to calculate the power of the assays to detect advanced liver fibrosis （AccuROC, Canada）. RESULTS： Serum concentrations of APO A-I, HPT and A2M were not significantly different in patients with chronic hepatitis B compared to controls. However, APO A-I level of 1.19 ng/L had a sensitivity of 85.7% and a specificity of 60.7% （AUC = 0.7117, P = 0.035） to predict advanced fibrosis. All other serum biochemical markers and their combination did not allow a useful prediction. None of these markers was a good predictor of histologic inflammation. CONCLUSION： Apolipoprotein A-I may be a suitable serum marker to predict advanced liver fibrosis in children with chronic hepatitis B.展开更多
Although localized prostate cancer(PCa)can be cured by prostatectomy and radiotherapy,the development of effective therapeutic approaches for advanced prostate cancer,including castration-resistant PCa(CRPC)and neuroe...Although localized prostate cancer(PCa)can be cured by prostatectomy and radiotherapy,the development of effective therapeutic approaches for advanced prostate cancer,including castration-resistant PCa(CRPC)and neuroendocrine PCa(NEPC),is lagging far behind.Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need.Here,we report that apolipoprotein A-I(ApoA-I),the major component of high-density lipoprotein(HDL),is upregulated in PCa based on both bioinformatics and experimental evidence.The fact that advanced PCa shows strong ApoA-I expression reflects its potential role in driving therapeutic resistance and disease progression by reprogramming the lipid metabolic network of tumor cells.Molecularly,ApoA-I is regulated by MYC,a frequently amplified oncogene in late-stage PCa.Altogether,our findings have revealed a novel indicator to predict prognosis and recurrence,which would benefit patients who are prone to progress to metastasis or even NEPC,which is the lethal subtype of PCa.展开更多
Apolipoprotein A-I (apoA-I), the principal apolipoprotein of high density lipoprotein (HDL) particle, has been the subject of intense investigation because of its
Background A low high-density lipoprotein cholesterol(HDL-C)to apolipoprotein A-I(apo A-I)ratio which reflects a small HDL-C particle size is emerging as an important predictor of cardiovascular risks.This study aimed...Background A low high-density lipoprotein cholesterol(HDL-C)to apolipoprotein A-I(apo A-I)ratio which reflects a small HDL-C particle size is emerging as an important predictor of cardiovascular risks.This study aimed to determine the association of HDL-C/apo A-I ratio with the severity of coronary artery lesions in diabetic patients.Methods Observational study was conducted and 478 diabetic patients with acute coronary syndrome(ACS)were enrolled.Baseline serum levels of HDL-C,apo A-I,clinical and biochemical parameters were collected.All patients underwent coronary angiography to evaluate the severity of coronary artery disease(CAD)in terms of the number of stenotic coronary arteries(defined as a stenosis≥50%)and the calculated Gensini score.Patients were then divided into different subgroups according to the two categories:single-,double-or triple-vessel groups;and Gensini Score groups(lower≤4,middle:5-15,and upper≥16).Receiver operating characteristic curves(ROC)were conducted to evaluate the diagnostic values in identifying severe CAD lesions.The association between HDL-C/apo A-I ratio and CAD severity was determined by multivariate logistic regression analysis.Results Patients with triple-vessel lesions or upper Gensini score had more CAD risk factors such as older age,smoking,low HDL-C and elevated fasting blood glucose(FBG).A lower HDL-C/apo A-I ratio corresponded to more vessels stenoses and a higher Gensini score.Notably,HDL-C/apo A-I outperformed HDL-C or apo A-I alone in diagnosing severe CAD lesions in ROC analyses.Moreover,multivariate regression analyses revealed that after adjustment for traditional risk factors such as LDL-C,FBG and HAb1c,HDL-C/apo A-I ratio remained independently associated with the severity of CAD in diabetic patients with ACS(all P<0.05).Conclusions HDL-C/apo A-I may be a useful indicator for the severity of CAD in diabetic patients with ACS.展开更多
The complete amino acid sequence of chicken plasma apolipoprotein(apo)A-I was determined by sequencing overlapping peptide fragments produced by trypsin,S.aureus V8 protease, and cyanogen bromide cleavage respectively...The complete amino acid sequence of chicken plasma apolipoprotein(apo)A-I was determined by sequencing overlapping peptide fragments produced by trypsin,S.aureus V8 protease, and cyanogen bromide cleavage respectively.All of the peptide fragments were purified on a Waters or on a Beckman HPLC system with a Vydae C_(18) column using 0.1% TFA in water as buffer A,and 0.08% TFA in 95% acetomtrile and 5% water as buffer B.Most of the peaks separated by these systems were pure.The partially purified fractions were subjected to rechromatography with a Hypersil ODS column using 0.005M sodium phosphate,pH 6.0,as buffer A,and 90% acetonitrile and 10% water as buffer B.The N-terminus of chicken apo A-I was determined to be aspartic acid by directly sequencing the intact protein up to 30 residues,while the C-terminus was identified as alanine by carboxypeptidase Y cleavage.There are 240 amino acid residues in mature chicken apo A-I.By direct analysis of cyanogen bromide peptide,we also determined the sequence of a 6 amino acid prosegment,which is present at approximately 10% of the molar amount of the mature protein in chicken plasma.展开更多
Background High-density lipoprotein cholesterol（HDL-C）levels are a strong,independent inverse predictor of coronary heart disease （CHD）.In this cross-sectional study we investigated the interrelationships between ...Background High-density lipoprotein cholesterol（HDL-C）levels are a strong,independent inverse predictor of coronary heart disease （CHD）.In this cross-sectional study we investigated the interrelationships between HDL-C and HDL relaled factors apolipoprotein A-I（apoA-I）and serum amyloid A（SAA）and the presence and extent of CHD in a population of Chinese patients with CHD. Methods Two hundred and twenty-four consecutive patients took part in this study.Demographic data were obtained from hospital records.Serum chemical concentrations were measured by standard laboratory methods.Reaults The concentrations of high-sensitive C-reactive protein（hsCRP）（median：1.85 mg/L）and SAP,（median：9.40 mg/L）were significantly higher in the CHD group（P〈0.05）,while concentrations of HDL-C（0.03±0.25）mmol/L）and apoA-I（（604.59±1 05.79）mmol/L）were significantly lower than those in the non-CHD group（P〈0.05）.The concentrations of apoA-l decreased with the increase in vascular damage.but the difference did not reach statistical significance.However, the concentrations of hsCRP and SAA increased with the increase in vascular damage.The unadjusted odd ratios（ORs）（CI） for apoA-I and SAA of the presence of CHD were 0.093（0.990-0.997）（P=0.00）and 2.571（1.029-6.424）（P〈0.05）,respectively.The association between elevated SAA and the presence of CHD was lost after adjusting for lipid status parameter concentrations.The associations between apoA-I.SAA and the extent of CHD remained strong,regardless of confounding variables.Conclusions Increased concentrations of SAA represent the inflammatory marker of the extent of coronary stenosis in patients with CHD.In contrast to SAA, the level of apoA-I was also associated with the presence of CHD, indicating that apoA-I was not only a marker of CHD presence but also a quantitative indicator of CHD extent.In short.determining the change apolipoprotein content within HDL particle is a more accurate and effective method to evaluate the impact of HDL on CHD.展开更多
Apolipoprotein A-I(Apo A-I),the main protein component of high-density lipoprotein(HDL),plays a pivotal role in reverse cholesterol transport(RCT).Previous studies indicated a reduction of serum Apo A-I levels in vari...Apolipoprotein A-I(Apo A-I),the main protein component of high-density lipoprotein(HDL),plays a pivotal role in reverse cholesterol transport(RCT).Previous studies indicated a reduction of serum Apo A-I levels in various types of cancer,suggesting Apo A-I as a potential cancer biomarker.Herein,ectopically overexpressed Apo A-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects,inhibiting cell proliferation and migration.Subsequent studies on the mechanism of expression regulation revealed that estradiol(E2)/estrogen receptorα(ERα)signaling activates Apo A-I gene transcription in breast cancer cells.Mechanistically,our Ch IP-seq data showed that ERαdirectly binds to the estrogen response element(ERE)site within the Apo A-I gene and establishes an acetylation of histone 3 lysine 27(H3 K27 ac)-enriched chromatin microenvironment.Conversely,Fulvestrant(ICI 182780)treatment blocked ERαbinding to ERE within the Apo A-I gene and downregulated the H3 K27 ac level on the Apo A-I gene.Treatment with p300 inhibitor also significantly decreased the Apo A-I messenger RNA(m RNA)level in MCF7 cells.Furthermore,the analysis of data from The Cancer Genome Atlas(TCGA)revealed a positive correlation between ERαand Apo A-I expression in breast cancer tissues.Taken together,our study not only revealed the antitumor potential of Apo A-I at the cellular level,but also found that ERαpromotes the transcription of Apo A-I gene through direct genomic effects,and p300 may act as a co-activator of ERαin this process.展开更多
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.
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.
文摘Background Alteration in the protein composition of high-density lipoprotein （HDL） has been proposed as a mechanism for the development of coronary heart disease （CHD）.In HDL,an increase in serum amyloid A protein （SAA） accompanying the decrease in apolipoprotein A-I （apoA-I） has been found during the acute inflammation period.However,whether this phenomenon persists in CHD patients,a disease related to inflammation,is unknown.The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients.Methods Overall,98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study.Potassium bromide （KBr） density gradient ultracentrifugation was used to isolate HDL from plasma.The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits.Pearson＇s correlation and general linear models were used in the analysis.Results Compared with controls,patients with CHD had a significant decrease in the amount of apoA-I （（14.21±8.44） μg/ml vs.（10.95±5.95） μg/ml,P =0.003） in HDL and a significant increase in the amount of log SAA （1.21±0.46 vs.1.51±0.55,P 〈0.00001）.Differences were independent of age,body mass index （BMI）,HDL cholesterol （HDL-C）,and other factors.An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group （β =2.0,P =0.026）.In the general linear model,changes in Iog（SAA）,age,age2,gender,BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I.Conclusions This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients,indicating the alteration of protein composition in HDL.However,the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.
文摘METHODS： We determined the serum level of apolipoprotein A-I （APO A-I）, haptoglobin （HPT） and a-2 macroglobulin （A2I） with an automatic nephelometer in 63 children （age range 4-17 years, mean 10 years） with biopsy-verified chronic HBeAg-positive hepatitis B. Fibrosis stage and inflammation grade were assessed in a blinded fashion according to Batts and Ludwig. We defined mild liver fibrosis as a score ≤2 and advanced fibrosis as a score equal to 3. ROC analysis was used to calculate the power of the assays to detect advanced liver fibrosis （AccuROC, Canada）. RESULTS： Serum concentrations of APO A-I, HPT and A2M were not significantly different in patients with chronic hepatitis B compared to controls. However, APO A-I level of 1.19 ng/L had a sensitivity of 85.7% and a specificity of 60.7% （AUC = 0.7117, P = 0.035） to predict advanced fibrosis. All other serum biochemical markers and their combination did not allow a useful prediction. None of these markers was a good predictor of histologic inflammation. CONCLUSION： Apolipoprotein A-I may be a suitable serum marker to predict advanced liver fibrosis in children with chronic hepatitis B.
基金This work is supported by the National Natural Science Foundation of China(No.81630019,81902611,and 81672522)Anhui Natural Science Foundation(1908085QH337).
文摘Although localized prostate cancer(PCa)can be cured by prostatectomy and radiotherapy,the development of effective therapeutic approaches for advanced prostate cancer,including castration-resistant PCa(CRPC)and neuroendocrine PCa(NEPC),is lagging far behind.Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need.Here,we report that apolipoprotein A-I(ApoA-I),the major component of high-density lipoprotein(HDL),is upregulated in PCa based on both bioinformatics and experimental evidence.The fact that advanced PCa shows strong ApoA-I expression reflects its potential role in driving therapeutic resistance and disease progression by reprogramming the lipid metabolic network of tumor cells.Molecularly,ApoA-I is regulated by MYC,a frequently amplified oncogene in late-stage PCa.Altogether,our findings have revealed a novel indicator to predict prognosis and recurrence,which would benefit patients who are prone to progress to metastasis or even NEPC,which is the lethal subtype of PCa.
文摘Apolipoprotein A-I (apoA-I), the principal apolipoprotein of high density lipoprotein (HDL) particle, has been the subject of intense investigation because of its
基金the National Key Research and Development Program of China(No.2016YFC1301202)National Key Research and Development Program of China(No.2016YFC1301305)。
文摘Background A low high-density lipoprotein cholesterol(HDL-C)to apolipoprotein A-I(apo A-I)ratio which reflects a small HDL-C particle size is emerging as an important predictor of cardiovascular risks.This study aimed to determine the association of HDL-C/apo A-I ratio with the severity of coronary artery lesions in diabetic patients.Methods Observational study was conducted and 478 diabetic patients with acute coronary syndrome(ACS)were enrolled.Baseline serum levels of HDL-C,apo A-I,clinical and biochemical parameters were collected.All patients underwent coronary angiography to evaluate the severity of coronary artery disease(CAD)in terms of the number of stenotic coronary arteries(defined as a stenosis≥50%)and the calculated Gensini score.Patients were then divided into different subgroups according to the two categories:single-,double-or triple-vessel groups;and Gensini Score groups(lower≤4,middle:5-15,and upper≥16).Receiver operating characteristic curves(ROC)were conducted to evaluate the diagnostic values in identifying severe CAD lesions.The association between HDL-C/apo A-I ratio and CAD severity was determined by multivariate logistic regression analysis.Results Patients with triple-vessel lesions or upper Gensini score had more CAD risk factors such as older age,smoking,low HDL-C and elevated fasting blood glucose(FBG).A lower HDL-C/apo A-I ratio corresponded to more vessels stenoses and a higher Gensini score.Notably,HDL-C/apo A-I outperformed HDL-C or apo A-I alone in diagnosing severe CAD lesions in ROC analyses.Moreover,multivariate regression analyses revealed that after adjustment for traditional risk factors such as LDL-C,FBG and HAb1c,HDL-C/apo A-I ratio remained independently associated with the severity of CAD in diabetic patients with ACS(all P<0.05).Conclusions HDL-C/apo A-I may be a useful indicator for the severity of CAD in diabetic patients with ACS.
文摘The complete amino acid sequence of chicken plasma apolipoprotein(apo)A-I was determined by sequencing overlapping peptide fragments produced by trypsin,S.aureus V8 protease, and cyanogen bromide cleavage respectively.All of the peptide fragments were purified on a Waters or on a Beckman HPLC system with a Vydae C_(18) column using 0.1% TFA in water as buffer A,and 0.08% TFA in 95% acetomtrile and 5% water as buffer B.Most of the peaks separated by these systems were pure.The partially purified fractions were subjected to rechromatography with a Hypersil ODS column using 0.005M sodium phosphate,pH 6.0,as buffer A,and 90% acetonitrile and 10% water as buffer B.The N-terminus of chicken apo A-I was determined to be aspartic acid by directly sequencing the intact protein up to 30 residues,while the C-terminus was identified as alanine by carboxypeptidase Y cleavage.There are 240 amino acid residues in mature chicken apo A-I.By direct analysis of cyanogen bromide peptide,we also determined the sequence of a 6 amino acid prosegment,which is present at approximately 10% of the molar amount of the mature protein in chicken plasma.
文摘Background High-density lipoprotein cholesterol（HDL-C）levels are a strong,independent inverse predictor of coronary heart disease （CHD）.In this cross-sectional study we investigated the interrelationships between HDL-C and HDL relaled factors apolipoprotein A-I（apoA-I）and serum amyloid A（SAA）and the presence and extent of CHD in a population of Chinese patients with CHD. Methods Two hundred and twenty-four consecutive patients took part in this study.Demographic data were obtained from hospital records.Serum chemical concentrations were measured by standard laboratory methods.Reaults The concentrations of high-sensitive C-reactive protein（hsCRP）（median：1.85 mg/L）and SAP,（median：9.40 mg/L）were significantly higher in the CHD group（P〈0.05）,while concentrations of HDL-C（0.03±0.25）mmol/L）and apoA-I（（604.59±1 05.79）mmol/L）were significantly lower than those in the non-CHD group（P〈0.05）.The concentrations of apoA-l decreased with the increase in vascular damage.but the difference did not reach statistical significance.However, the concentrations of hsCRP and SAA increased with the increase in vascular damage.The unadjusted odd ratios（ORs）（CI） for apoA-I and SAA of the presence of CHD were 0.093（0.990-0.997）（P=0.00）and 2.571（1.029-6.424）（P〈0.05）,respectively.The association between elevated SAA and the presence of CHD was lost after adjusting for lipid status parameter concentrations.The associations between apoA-I.SAA and the extent of CHD remained strong,regardless of confounding variables.Conclusions Increased concentrations of SAA represent the inflammatory marker of the extent of coronary stenosis in patients with CHD.In contrast to SAA, the level of apoA-I was also associated with the presence of CHD, indicating that apoA-I was not only a marker of CHD presence but also a quantitative indicator of CHD extent.In short.determining the change apolipoprotein content within HDL particle is a more accurate and effective method to evaluate the impact of HDL on CHD.
基金supported by the National Natural Science Foundation of China(Nos.81672785,31871291,and82073113 to Li TAN)the National Key R&D Project of China(No.2016YFA0101800 to Li TAN)supported by the Innovative Research Team of High-level Local University in Shanghai。
文摘Apolipoprotein A-I(Apo A-I),the main protein component of high-density lipoprotein(HDL),plays a pivotal role in reverse cholesterol transport(RCT).Previous studies indicated a reduction of serum Apo A-I levels in various types of cancer,suggesting Apo A-I as a potential cancer biomarker.Herein,ectopically overexpressed Apo A-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects,inhibiting cell proliferation and migration.Subsequent studies on the mechanism of expression regulation revealed that estradiol(E2)/estrogen receptorα(ERα)signaling activates Apo A-I gene transcription in breast cancer cells.Mechanistically,our Ch IP-seq data showed that ERαdirectly binds to the estrogen response element(ERE)site within the Apo A-I gene and establishes an acetylation of histone 3 lysine 27(H3 K27 ac)-enriched chromatin microenvironment.Conversely,Fulvestrant(ICI 182780)treatment blocked ERαbinding to ERE within the Apo A-I gene and downregulated the H3 K27 ac level on the Apo A-I gene.Treatment with p300 inhibitor also significantly decreased the Apo A-I messenger RNA(m RNA)level in MCF7 cells.Furthermore,the analysis of data from The Cancer Genome Atlas(TCGA)revealed a positive correlation between ERαand Apo A-I expression in breast cancer tissues.Taken together,our study not only revealed the antitumor potential of Apo A-I at the cellular level,but also found that ERαpromotes the transcription of Apo A-I gene through direct genomic effects,and p300 may act as a co-activator of ERαin this process.
