Apolipoprotein B and ischemic stroke / 国际脑血管病杂志

Studies have shown that plasma apolipoprotein B (ApoB) has a good predictive value for ischemic stroke and plays an important role in the prevention and treatment of ischemic stroke. More and more guidelines and consensus opinions began to recommend ApoB as a routine intervention target. This article reviews the biological characteristics, clinical detection advantages, and role and treatment prospect of ApoB in the prevention and treatment of ischemic stroke.

Analysis of small dense low-density lipoprotein cholesterol level and the relationship with corresponding lipid components in healthy adults / 中华检验医学杂志

Objective:To investigate the small and dense low density lipoprotein cholesterol (sdLDL-C) level, ratios of sdLDL-C/low density lipoprotein cholesterol (LDL-C), sdLDL-C/high density lipoprotein cholesterol (HDL-C) and sdLDL-C/apolipoprotein B (apoB), and their correlation with lipid components in healthy adults.Methods:A total of 1 151 healthy adults, who underwent physical examination in Beijing Anzhen Hospital Affiliated to Capital Medical University from September to December 2020 (557 men and 594 women), were included in this study. They were divided into five age groups: 18-29 years old ( n=247), 30-44 years old ( n=269), 45-59 years old ( n=225), 60-74 years old ( n=207) and 75-90 years old ( n=203) according to the age classification standard of the United Nations World Health Organization in 2018. The levels of total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, sdLDL-C, apoA1 and apoB were measured, and the distribution of sdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB in different sex and age groups were analyzed. Pearson/Spearman correlation was used to analyze the correlation between the above four indexes and other blood lipid components. Results:SdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB were higher in male group ([0.56±0.23] mmol/L, 0.24±0.07, 0.49±0.22, 0.27±0.07) than those in female group ([0.48±0.18] mmol/L, 0.20±0.06, 0.36±0.17, 0.23±0.07) (all P<0.01). SdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB were different among different age groups of male and female participants (all P<0.001). SdLDL-C level was significantly higher in males than in females among 18-29 years old group, 30-44 years old group, 45-59 years old group (all P<0.05). SdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB were higher in males of 18-29 years old group, 30-44 years old group, 45-59 years old group and 60-74 years old group than in females of corresponding age groups (all P<0.05). The level of sdLDL-C of all participants was positively correlated with TC, TG, LDL-C, apoB, non-HDL-C and remnant cholesterol ( r＝0.50, 0.45, 0.67, 0.68, 0.61, 0.11, all P<0.01), and negatively correlated with HDL-C and apoA1 ( r＝-0.17 and -0.10, P<0.01). Conclusions:The levels of sdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB in healthy adults are different in healthy adults of different ages and sex. There is a high correlation between sdLDL-C and apoB.

Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Predictive value of apolipoprotein B in the risk of progression to renal replacement therapy in diabetic kidney diseases patients / 中华肾脏病杂志

Objective To analyze the predictive value of apolipoprotein B (ApoB) in the risk of progression to renal replacement therapy (RRT) in diabetic kidney disease (DKD) patients with chronic kidney disease (CKD) stage 3-5. Methods The data of DKD patients with CKD stage 3-5 who were hospitalized and followed up with detailed clinical data from January 2011 to November 2014 in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively collected. Estimated glomerular filtration rate (eGFR) was calculated according to the CKD-EPI formula. After 2 years of follow-up, the patients were divided into RRT group and non-RRT group according to whether they had entered renal replacement therapy. Cox regression analysis was used to analyze the influencing factors of DKD progression to RRT. The predicted value of ApoB in the risk of progression to renal replacement therapy (RRT) of DKD patients within 2 years of follow-up was analyzed by plotting the receiver operating characteristic curve (ROC). By establishing multiple Cox models, the effect of ApoB elevation on the progression of DKD patients to RRT was analyzed after adjusting for the influencing factors gradually. Results A total of 258 cases were included in this study, including 156 males and 102 females. They were (66.13±11.88) years old (27-91 years old). CKD 3-5 patients were 181 cases, 50 cases and 27 cases respectively. There were 165 cases in the non-RRT group and 93 cases in the RRT group. There were statistically significant difference in hemoglobin, hematocrit, blood phosphorus, ApoB, serum creatinine, urea nitrogen, serum cystatin C, eGFR and in the proportion of using angiotensin converting enzyme inhibitor, diuretic, β blockers between the two groups (all P＜0.05). Multivariate Cox regression analysis showed that ApoB was an independent predictor of progression to RRT in patients with DKD within 2 years (HR=2.203, 95% CI 1.352-3.589, P=0.002). The area under the ROC curve of ApoB for DKD progression to RRT within 2 years of follow-up was 0.641 (C-index=0.749, P＜0.01). After adjusting for confounding factors, Cox regression analysis showed that for every 1 mmol/L increase in ApoB, the risk of RRT increased by 1.038 times in DKD patients with CKD stage 3-5 (HR=2.038, 95% CI 1.312-3.168, P=0.002). Conclusions ApoB is an independent predictor of progression to RRT with CKD stage 3-5 diabetic kidney disease (DKD). For every 1 mmol/L increase in ApoB, the risk of progression to RRT in patients with CKD 3-5 DKD increases by 1.038 times.

Peptides releasing study of serum apolipoprotein A-I and apolipoprotein B by ID-LC-MS / 中华检验医学杂志

Objective To investigate the digestion kinetics of Apolipoprotein A-I and B by ID-LC-MS method for accurate quantification of proteins .Methods Methodological research .The target peptides of ApoA-I and B were determined .The ApoA-I and B from 5 human serum samples on market with levels from 0.90-2.54 g/L and 0.54-1.39 g/L separately , were measured in terms of target peptides by isotope dilution liquid chromatography mass spectrometry method .The releasing amount and rate of peptides were analyzed and plotted according to different time points .The correlation coefficient R2 was calculated among peptide releasing amount between samples .Results Most peptides reached their peaks within 4 hours.The peptides VQ , DY and VS from Apo A-I, TR and FP from Apo B were released relatively slowly .After getting to their peak stage , the ratio between TEV and SIL-TEV, AK and SIL-AK, VQ and SIL-VQ presented stable state.As for Apo A-I the correlations among peptides are high , from 0.904 to 0.999.Some peptides from Apo B show lower correlations , such as TG-SV with R20.543 (3 h).Conclusions Peptides from Apo A-I and Apo B present different releasing properties after trypsin digestion .Proper selection of representative peptides and enzymatic conditions can benefit accurate quantification of target proteins .

Interaction between APOB gene polymorphism and risk factors in coronary heart disease patients without lipid-lowering treatment / 中华心血管病杂志

Objective@#To investigate the association between APOB gene R532W polymorphism and the risk of coronary heart disease (CHD) in patients without lipid-lowering treatment and to analyze the interactions between the variation of R532W and different risk factors of CHD.@*Methods@#CHD and non-CHD were diagnosed according to coronary artery angiography (CAG) and/or coronary computed tomography angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD patients and 772 age- and sex-matched non-CHD controls, who never accepted any lipid-lowering treatments, were collected. R532W was genotyped by HumanExome BeadChip at BGI and strict quality control was made. Firstly, the association between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG, AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was explored. Then, the interactions between the variation of this loci and risk factors related to CHD were investigated.@*Results@#(1) Total cholesterol (TC) levels were significantly lower in AA genotype than in GA genotype in the total cohort and non-CHD controls, but was similar among the 3 genotypes in CHD patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532 polymorphism was related to the incidence of CHD in the dominant model, and A-allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI 0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W polymorphism had positive interactions with hypertension (1.452) and smoke (1.077), while negative interaction with diabetes (0.553) in the occurrence of CHD.@*Conclusions@#APOB gene R532W polymorphism is related to TC levels in Chinese north Han population. A-allele carries of R532W loci is linked with reduced risk of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a positive additive interaction with hypertension and smoke, while a negative additive interaction with diabetes mellitus in the occurrence of CHD.

Hipobetalipoproteinemia primária: relato de caso / Primary Hypobetalipoproteinemia: a case report

Descrevemos o caso de uma paciente de 19 anos diagnosticada com hipobetalipoproteinemia primária. A paciente apresentava sintomas compatíveis com a doença como diarreia desde o primeiro mês de vida, défice de crescimento e retinopatia. A biópsia duodenal evidenciou presença de vacúolos lipídicos intraepiteliais, os quais foram altamente sugestivos para o diagnóstico. Os exames complementares evidenciaram disfunção hepática, baixos níveis séricos de triglicerídeos, e de colesterol total e frações. Após a dosagem de apolipoproteína B abaixo dos valores da normalidade, aliada a clínica e exames complementares, o diagnóstico foi realizado. A relativa escassez de dados na literatura em nosso meio, atrelada à raridade da doença, ilustra a relevância deste relato de caso, somado à importância do diagnóstico precoce

The case of a 19-year-old female patient who was diagnosed with Primary Hypobetalipoproteinemia (HBL) is described.The patient presented symptoms that were consistent with the disease, such as diarrhea from the very first month of life, growth failure and retinopathy. The duodenal biopsy showed the presence of intraepithelial lipid vacuoles that were highly suggestive of the diagnosis. Further tests showed liver dysfunction, low serum levels of triglycerides and total cholesterol and fractions. After the dosage of Apolipoprotein B below normal values, and clinical exam along with laboratory tests, the diagnosis was made. The lack of data in the literature and the rarity of the disease illustrate the importance of this case report,and of an early diagnosis.

Expressions of APOBEC3s in HaCaT keratinocytes carrying the genome of human papillomavirus type 11 and regulatory effects of interferon-alpha on the expressions / 中华皮肤科杂志

Objective To investigate mRNA expressions of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 family (APOBEC3s or A3s) as well as expressions and subcellular distribution of major A3 proteins in HaCaT keratinocytes carrying the genome of human papillomavirus type 11 (HPV11.HaCaT),and to evaluate regulatory effects of exogenous interferon-alpha (IFN-α) on the expressions of A3s.Methods The basal levels of A3A,A3B,A3C and A3H mRNA expressions were measured by real-time fluorescence-based quantitative PCR (qRT-PCR) in HPV11.HaCaT cells and normal HaCaT cells.Cultured HaCaT,HPV11.HaCaT and Hela cells were treated with recombinant human IFN-α 2b (rhIFN-α2b) at concentrations of 104,105 and 106 IU/ml for 6,24 and 48 hours separately,and those receiving no treatment served as the normal control groups.Then,qRT-PCR was performed to measure mRNA expressions of A3A,A3B,A3C and A3H in these cells.Immunofluorescence staining was conducted to observe the expression and distribution of A3A protein in cells after the treatment with rhIFN-α2b for 6 hours.Results As qRT-PCR showed,the basal levels of A3A,A3B and A3C mRNA expressions were all significantly higher in HPV11.HaCaT cells than in normal HaCaT cells (all P ＜ 0.05).After stimulation,the mRNA expressions of the four A3 members increased to different extents with the increase in rhIFN-α2b concentrations,and the increase in A3A mRNA was the most significant.Compared with corresponding normal control groups,the mRNA expression of A3A was significantly increased in HaCaT cells (35.77 ± 5.01 vs.1.00 ± 0.05,P ＜ 0.05),HPV 11.HaCaT cells (15.34 ± 2.14 vs.0.99 ± 0.01,P ＜ 0.05) and Hela cells (24.60 ± 5.45 vs.0.97 ± 0.03,P ＜ 0.05) after the treatment with rhIFN-α2b at 106 IU/ml for 6 hours,while the increase in A3B,A3C and A3H mRNA expressions was no more than 9-fold in these cell lines after that.Enhanced staining for A3A was observed in nuclei and cytoplasm of the 3 cell lines after the treatment with rhIFN-α2b at 106 IU/ml for 6 hours.Conclusions HPV11 transfected into HaCaT cells can activate intracellular A3s,especially A3A.IFN-α may play an immunoregulatory role by inducing high levels of A3A expression.

Level of apolipoprotein and other related indicators in adults in Hunan province / 中国医师杂志

Objective To investigate the levels and the abnormal incidences of apolipoprotein and other related indicators in health people in Hunan province,and to provide data for establishment of reference intervals in Hunan province.Methods The people with physical examination (n =341) were chosen from the Second Xiangya Hospital of Central South University during August 2014 ～ October 2014 (male,n =239;female,n =102) with age from 22 to 77 years old.All people were divided into 4 groups according to their age:group A aged from 22 to 42 (35.56 ± 5.39),group B aged from 43 to 48 (45.59 ± 1.59),group C aged from 49 to 55 (51.19 ± 1.81),and group D aged from 56 to 77 (63.08 ±5.84).The levels of apoAI,apoB,Lp (a),hypersensitive C-reactive protein (hs-CRP),and homocysteine (HCY) were detected with automatic biochemical analyzer,and were compared among different age groups and between male and female in each age group.Results Compared to male,the average levels of apoAI,and Lp (a) were significantly increased (P ＜0.05),and apoB,hs-CRP,and Hcy were significantly decreased (P ＜ 0.05) in the female.The levels of apoB,and hs-CRP were significantly different among 4 age groups (P ＜ 0.05).The abnormal rate in each index among 4 age groups was not significantly different (P ＞ 0.05).For groups A,B and D,the abnormal rate of Hcy was significant higher in male relative to female (P ＜ 0.05).Conclusions All the indices have significant difference between male and female (P ＜0.05).The levels of apoAI,Lp (a),hs-CRP,and Hcy do not change with the changed age.However,apoB has a certain relationship with age.The level and abnormal rate of Hcy are significantly higher in male relative to female.

Correlation between apolipoprotein B/apolipoprotein A-Ⅰ and intracranial artery stenosis in young patients with ischemic stroke / 国际脑血管病杂志

Objective To investigate the relationship between the serum apolipoprotein B (ApoB)/ ApoA-Ⅰ ratio and intracranial artery stenosis in young patients with ischemic stroke.Methods Patients with ischemic stroke aged from 18 to 45 were enrolled in the study.Brain CT angiography was used to evaluate the degree of intracranial artery stenosis,and the concentrations of serum total cholesterol,triglyceride,highdensity lipoprotein cholesterol,low-density lipoprotein cholesterol,ApoA-Ⅰ,and ApoB were detected.The ratio of ApoB/ApoA-Ⅰ was calculated.The Demographic and clinical characteristics of the intracranial artery stenosis group and the non-intracranial artery stenosis group were compared.Multivariate logistic regression analysis was used to identify the independent risk factors for intracranial artery stenosis in young patients with ischemic stroke.Results A total of 161 young patients with ischemic stroke were enrolled,including 89 in the intracranial artery stenosis group and 72 in the non-intracranial artery stenosis group.The constituent ratios of diabetes mellitus (20.2％ vs.6.9％;x2 =4.641,P =0.032),smoking (47.5％ vs.15.2％;x2 =15.121,P=0.001),hyperlipidermia (56.1％ vs.48.6％;x2 =4.197,P=0.040),as well as the radios in serum high-density lipoprotein cholesterol (1.29 ± 0.30 mmol/L vs.1.65 ± 0.34 mmol/L;t =7.131,P=0.002),ApoA-Ⅰ (1.49 ± 0.65 g/L vs.1.63 ± 0.23 g/L;t =2.751,P =0.001),ApoB (1.49 ± 0.65 g/L vs.1.63±0.23 g/L;t=2.751,P=0.001),and ApoB/ApoA-Ⅰ ratio (1.49±0.65 vs.1.63± 0.23;t =2.751,P=0.001) had significant differences between the two groups.Multivariate logistic regression analysis showed that diabetes (odds ratio [OR] 3.052,95％ confidence interval [CI] 1.186-7.856;P =0.021),smoking (OR 2.997,95％ Cl 1.456-6.172;P =0.003),hyperlipidemia (OR 4.745,95％ CI 2.108-10.668;P =0.001),ApoB (OR 4.861,95％ CI 3.029-7.802;P=0.001),and ApoB/ ApoA-Ⅰ ratio (OR 5.684,95％ CI 2.215-14.584;P=0.002) were the independent risk factors for intracranial artery stenosis in young patients with ischemic stroke,while HDL-C (OR 0.561,95％ CI 0.354-0.888;P=0.014) and ApoA-Ⅰ (OR 0.065,95％ CI 0.010-0.409;P=0.004) were the independent protective factors.After adjustment for hypertension,diabetes,smoking,hyperlipidemia,HDL-C,ApoA-Ⅰ,and ApoB,ApoB/ApoA-Ⅰ ratio was still an independent risk factor for intracranial artery stenosis in young patients with ischemic stroke (each increase of 1 standard deviation,OR 4.255,95％ CI 2.348-7.711;P=0.001).Conclusion ApoB/ApoA-Ⅰ ratio is an independent risk factor for intracranial artery stenosis in young patients with ischemic stroke.

Relationship between ApoB gene Msp I/Xba I/EcoR I polymorphisms and serum lipid level in male Han population in Chongqing, China / 第二军医大学学报

Objective To explore the relationship between apolipoprotein B (ApoB) gene MspI/XbaI/EcoRI polymorphisms and the levels of serum lipid in male Han population in Chongqing. Methods The ApoB gene MspI/XbaI/EcoRIpolymorphisms were detected by gene chip technology in 157 dyslipidemia cases and 180 healthy controls; and their relationship with serum lipids was analyzed in the dyslipidemia group and the controls. Results In both dyslipidemia group and control group, the total cholesterol (TC) levels with M+M- genotype at MspI locus were significantly higher than those with M+M+ genotype (dyslipidemia group: [6.54±0.58] vs [5.58±0.83] mmol/L, P<0.01; control group: [5.43±0.17] vs [4.39±0.62] mmol/L, P<0.01); the high density lipoprotein cholesterol (HDL-C) levels with X+X- genotype at XbaI locus were significantly lower than those with X-X- genotype, whereas the low density lipoprotein cholesterol (LDL-C) levels were significantly higher than those with X-X- genotype (dyslipidemia group HDL-C: [1.08±0.27] vs [1.22±0.44] mmol/L, P=0.03; LDL-C: [3.88±0.63] vs [3.46±0.83] mmol/L, P=0.01; control group HDL-C: [1.31±0.43] vs [1.48±0.37] mmol/L, P=0.04; LDL-C: [3.19±0.54] vs [2.94±0.59] mmol/L,P=0.02); the HDL-C levels with E+E- genotype at EcoRI locus were significantly lower than those with E+E+ genotype (dyslipidemia group: [1.01±0.18] vs [1.21±0.43] mmol/L, P=0.01; control group: [1.27±0.20] vs [1.47±0.40] mmol/L, P=0.03). The HDL-C levels in dyslipidemia group with X+X- genotype were significantly lower than the control group with X+X- genotype, but the LDL-C levels were significantly higher than the control group with X+X- genotype (HDL-C: [1.08±0.27] vs [1.31±0.43] mmol/L, P=0.01; LDL-C: [3.88±0.63] vs [3.19±0.54] mmol/L,P<0.01); the HDL-C levels in the dyslipidemia group with E+E- genotype were significantly lower than those in the control group ([1.01±0.18] vs [1.27±0.20] mmol/L, P<0.01). The multiple linear regression analysis showed that ApoB gene MspI polymorphism was positively correlated with TC; XbaIpolymorphism was negatively correlated with HDL-C and positively correlated with LDL-C. Conclusion The ApoBgene MspI and XbaI polymorphisms may be associated with the levels of serum lipids. There is a tendency that the M+M- genotype can increase TC levels and the X+X- genotype can reduce HDL-C levels and increase LDL-C levels.

Association of Apolipoprotein B/Apolipoprotein A1 Ratio and Coronary Artery Stenosis and Plaques Detected by Multi-Detector Computed Tomography in Healthy Population

Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.

Effects of acute knockdown of hepatic insulin receptor on secretion of apolipoprotein B and triglyceride in mice / 中华老年医学杂志

Objective To analyze the effects of acute depletion of liver-specific insulin signaling on secretion of apolipoprotein B (apoB) and triglyceride (TG).Methods Based on Cre-LoxP principle,a promoter of hepatic tissue specific albumin gene was inserted into upstream of the cre recombinase gene.Albumin-Cre adenovirus (Ad-CRE) and GFP adenovirus (Ad-GFP) were amplified in 293A cells and purified before intravenous administration to mice.After adenovirus infection for 2 days,4 days and 6 days,blood samples from mice were collected and hepatic tissues were frozen.The secretion rates of hepatic newly synthesized apoB and very low density lipoprotein (VLDL)-TG were determined by injection of Triton WR-1339.The levels of plasma cholesterol (TC) and TG were measured.The expressions of insulin receptor and other lipoprotein metabolism related proteins in hepatic tissues were analyzed by Western blot.Results After 2 d,4 d and 6 d of the Ad-CRE injection into mice,insulin receptor expression was reduced by 30.50％ (P＜0.05),60.12％ (P＜ 0.01) and 99.54％ (P＜0.001),and VLDL-TG secretion rate was decreased by 20.43％ (P＜0.05),33.63％ (P＜0.05) and 44.21％ (P＜0.01),respectively.Expressions of sterol regulatory binding proteins 1,fatty acid synthase,and the related proteins of VLDL-formation were decreased,but there were no changes in hepatic secretion of apoB100 and hepatic lipids.The hepatic secretion of apoB48 was increased by 35.07％ (P＜0.05) 6 d after Ad-CRE injection.Conclusions Acute depletion of hepatic insulin receptor might reduce VLDL-TG secretion in manner of time-dependent,and increase the assembly and secretion of smaller apoB-containing lipoproteins in mice liver,which is probably associated with decreased lipogenesis.

Clinical Impact of Non-High Density Lipoprotein-Cholesterol and Apolipoprotein B on Clinical Outcomes in Metabolic Syndrome Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: Non-high density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (ApoB) are markers of atherosclerotic risk and predictors of cardiovascular events. The aim of this study was to evaluate clinical impact of non-HDL-C and ApoB on clinical outcomes in metabolic syndrome (MS) patients with acute myocardial infarction (AMI) undergoing percuatneous coronary intervetion. SUBJECTS AND METHODS: We analyzed 470 MS patients (64.4+/-12.0 years, 53.6% male) with AMI who were followed-up for 12-month after percutaneous coronary intervention (PCI) from December 2005 to January 2008 in a single center. These patients were divided into 2 groups based on median values of non-HDL-C and ApoB. We studied their baseline and follow-up relation with 12-month clinical outcomes, all-cause death and major adverse cardiac events (MACE). RESULTS: Mean values of baseline non-HDL-C and ApoB were 141.2+/-43.1 mg/dL and 99.3+/-29.0 mg/dL respectively. During 12-month follow-up 32 MACE (6.8%) and 12 deaths (2.5%) occurred. We observed significant correlation between non-HDL-C and ApoB. Twelve-month MACE and all-cause death after PCI showed no significant relation as non-HDL-C or ApoB levels increased. Follow-up patients (n=306, rate 65%) also did not show significant relation with clinical outcomes. Twelve-month MACE decreased as non-HDL-C and ApoB reduction rates increased. CONCLUSION: There was no significant association between higher non-HDL-C or ApoB and 12-month clinical outcomes in MS patients with AMI undergoing PCI. ApoB was found to be a better predictor of 12-month MACE than non-HDL-C based on their reduction rates.

Factores de riesgo cardiovascular y perfil apolipoprotéico en un grupo de adultos atendidos en un centro público de salud del estado Carabobo, Venezuela / Cardiovascular risk factors and apolipoproteic profile in a group of adults treated in a public health center in Carabobo state, Venezuela

Objetivos. Comparar los niveles séricos de las apolipoproteínas A-I y B así como las relaciones Apo B/Apo A-I y HDL colesterol/Apo A-I según edad, sexo y factores de riesgo cardiovascular en individuos atendidos en un centro público de salud venezolano. Materiales y métodos. Se determinó la presión arterial, la circunferencia de cintura (CC), el perfil lipídico y las apolipoproteínas A-I y B en 221 individuos (44,0±15,5 años) de ambos sexos; también se calculó el índice de masa corporal (IMC) a partir del peso y la talla y se estableció hábito al tabaco, la ingesta de bebidas alcohólicas y el patrón de su consumo. Resultados. El 27,5 por ciento presentó concentraciones bajas de Apo A-I, 45,2 por ciento Apo B elevada y 60,6 por ciento relación Apo B/Apo A-I alta. Los niveles séricos de las apolipoproteínas y la relación Apo B/Apo A-I no variaron con la edad o sexo, mientras que la relación HDL colesterol/Apo A-I disminuyó al elevarse la edad. Los individuos obesos, fumadores, hipertensos, hipercolesterolémicos, hipertrigliceridémicos o con HDL colesterol bajo mostraron cifras más elevadas de Apo B y Apo B/Apo A-I. La relación HDL colesterol/Apo A-I disminuyó con la edad, el nivel de habito al tabaco y el aumento de LDL-C y triglicéridos. El consumo de tres o más bebidas alcohólicas/día se asoció con disminución de Apo B. Conclusiones. Se demostró alta prevalencia de perfil apolipoprotéico alterado, lo cual se asoció con los principales factores de riesgo cardiovascular. Los resultados del estudio apoyan la inclusión de las apolipoproteínas evaluadas en las determinaciones de laboratorio realizadas en los centros públicos de atención de salud venezolanos.

Objectives. To compare serum levels of apolipoproteins A-I and B as well as Apo B/Apo A-I and HDL cholesterol/Apo A-I ratios by age, gender and cardiovascular risk factors in individuals treated at a Venezuelan public health center. Materials and methods. We determined in 221 individuals (44.0 ± 15.5 years) of both genders blood pressure, waist circumference (WC), lipid profile and apolipoproteins A-I and B; body mass index (BMI) was calculated from weight and height; smoking habit, alcohol intake and consumption pattern were established. Results. 27.5 percent of individuals had low levels of Apo A-I, 45.2 percent high Apo B and 60.6 percent high Apo B/Apo A-I ratio. Serum levels of apolipoproteins and Apo B/Apo A-I ratio did not vary with age or gender, while the ratio HDL cholesterol/Apo A-I decreased with the age. Obese individuals, smokers, hypertensive, hypercholesterolemics, hypertriglyceridemics or with low HDL cholesterol showed higher Apo B and Apo B/Apo A-I ratio. Older individuals, smokers or individuals with increased LDL cholesterol and triglycerides showed lower HDL cholesterol/Apo A-I ratio. Consumption of three or more alcoholic drinks/day was associated with decreased Apo B. Conclusions. These results show high prevalence of altered apolipoprotein profile, which is associated with major cardiovascular risk factors. The results support the inclusion of the evaluated apolipoproteins in laboratory determinations made in public health centers in Venezuela.

Tratamento da hipercolesterolemia: quais os mais importantes produtos de pesquisa? / Hypercholesteromia the most important products being researched?

As estatinas são produtos farmacêuticos de grande sucesso em todo mundo. Entretanto, muitos pacientes, ou por não as tolerarem adequadamente, ou por necessitarem de taxas mais baixas de LDL-colesterol estabelecidas como metas, poderão ter benefícios clínicos com o emprego de novos medicamentos. Numerosas linhas de pesquisa encontram-se em evolução, avaliando produtos com atuação em diferentes vias moleculares: inibidores de síntese da apolipoproteína B, inibidores da DGAT2, da ACAT2, da MTP, da esqualeno sintase, tireoidemiméticos e inibidores da PCSK9. Espera-se, para futuro próximo, a introdução no mercado desses medicamentos, que poderão auxiliar ainda mais na prevenção primária e secundária da doença aterosclerótica coronária, flagelo deste novo século.

Statins are pharmaceutical products that obtained worldwide success. However, some patients with inadequate tolerability to these medications and the need of achieving lower LDL-cholesterol levels as recommended targets, may receive clinical benefits with the use of new drugs. Many research lines have been in evolution evaluating products that act in different molecular pathways: inhibitors of apoliprotein B synthesis, inhibitors of DGAT2, ACAT2, MTP, squalene synthase, thyromimetics, and inhibitors of PCSK9. It is a hope that the future introduction of many of these products on the market will help furthermore primary and secondary prevention of coronary heart disease, a scourge of this new century.

Apolipoprotein B is Highly Associated with the Risk of Coronary Heart Disease as Estimated by the Framingham Risk Score in Healthy Korean Men

The aim of this study was to examine the association between serum apolipoprotein B (apoB) and the risk of coronary heart disease (CHD) using Framingham risk score (FRS) in healthy Korean men. A total of 13,523 men without medication history of diabetes and hypertension were enrolled in this study. The FRS is based on six coronary risk factors. FRS > or = 10% was defined as more-than-a-moderate risk group and FRS > or = 20% as high risk group, respectively. The logistic regression analyses were conducted. When quartile 1 (Q1) set as a reference, in unadjusted analyses, the Q2, Q3, Q4 of apoB level had increased odds ratio (OR) for the risk of CHD in both more-than-a-moderate risk and high risk group, respectively. After adjusting for confounding variables, multivariable-adjusted logistic regression analyses showed a strong relationship between the quartiles of apoB level and more-than-a-moderate risk and high risk group, respectively. These associations were attenuated, but still remained statistically significant. ApoB is found to be independently related to the risk of CHD using FRS in healthy Korean men, and the link between apoB and the risk of CHD is dose-depedent.

Association of EcoRI and XbaI polymorphisms of apolipoprotein B gene with dyslipidemia and lipid levels / 中国医师杂志

Objective To explore the association of apoB gene polymorphisms with dyslipidemia and lipid levels in Xinjiang Shihezi Han Chinese. Methods 150 dyslipidemia patients and 150 normal pople were involved in this study. EcoRI and XbaI polymorphisms of apolipoprotein B was analyzed by PCR-restriction fragment length polymorphism. The levels of plasma total cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apoAI and apoB were determined. Results The frequency of E + E -/E - E - genotype and E-Allele(37.3% and 19% ) in dyslipidemia group was significantly higher than that in controls( 12. 7% and 6. 3% ). The levels of TC, TG and LDL-C in the E +E -/E - E - gene type were significantly higher than those of the E + E + gene type in each group ( P ＜0. 01 ). The frequency of X + X -/X + X + genotype and X + Allele( 20. 7% and 1 1% ) in dyslipidemia group was significantly higher than that in controls (8% and 4% ). The levels ofTC, TG, LDL-C and apoB in the X + X -/X + X + gene type patients were significantly higher than those in the X - X - gene type patients in every group ( P ＜ 0. 05 ). Conclusion The EcoRI and XbaI polymorphism of ApoB gene was related to dyslipidemia in population of Xinjiang Shihezi Han Chinese, and the E - and X + Allele may be the genetic risk factors for dyslipidemia.

The Haplotype Analyses Using Multiple Markers of the Apolipoprotein B Gene in Patients with Coronary Artery Disease

The high level of low density lipoprotein (LDL) is a risk factor for cardiovascular disease. Apolipoprotein (apo) B is a major protein component of LDL and plays an important role in the maintenance of cholesterol homeostasis. In this study, six polymorphic sites of the apoB gene were anlaysed in 235 patients with coronary artery disease (CAD) and 216 normal control subjects. There were no significant differences in the allele frequencies of apoB polymorphisms between the control and patient groups. However, haplotype frequencies were significantly different between the CAD patients and control (p<0.05). In addition, the allelic distributions of both EcoRI and MspI polymorphisms in Koreans were similar to those in Chinese but significantly different from those in Caucasians. ApoB polymorphisms showed no association with plasma lipid levels. In conclusion, haplotype analysis of the apoB gene using multiple diallelic markers might be a useful marker for Korean CAD patients.

THE EFFECT OF APOLIPOPROTEIN B POLYMORPHISMS ON THE LIPID REGULATING THERAPY FOR HYPERLIPIDEMIA / 解放军医学杂志

To study the efficacy of small dosage of simvastatin on the treatment of hyperlipidemia, and the effect of polymorphisms in ApoB gene expression. Sixty one patients with hyperlipidemia were selected and simvastatin 5mg/d was used. TC, TG, HDL, LDL, ApoAI and ApoB and the function of liver and kidney were measured in every patient prior to the treatment and 4, 8, 12 weeks after treatment. RFLPs was applied for determination of polymorphisms on Xbal locus of the ApoB gene. In the total of 61 patients, X + X - genotype was found in 5 patients (8.20%), and X - X - genotype in 56 patients (91.80%), but no X + X + genotype was found. The relative frequency of X + allele was 0.041, and X - allele was 0.959, suggesting X - allele was still a dominant one in the patients with hyperlipidemia. The results showed that small dosage of simvastatin could effectively reduce blood levels of TC, TG, LDL C and ApoB. The levels of TC and LDL C lowering was more prominent in X - X - genotype than that in X + X - genotype (27.62% and 35.02% vs. 22.36% and 20.05%, P