Hypertriglyceridemia promotes dysfunctions in high-density lipoprotein increasing the cardiovascular risk

Abstract Hypertriglyceridemia is associated with several metabolic diseases. The triglycerides (TG) disrupt the cholesterol reverse transport and contribute to increased levels of low-density lipoprotein (LDL). High-density lipoprotein (HDL) acts in cholesterol reverse transport as an anti-inflammatory and antioxidant. This study aims to investigate the role of hypertriglyceridemia in the functionality of HDL. Individuals were divided into 4 groups based on high or low HDL-c and triglycerides levels. Biochemical and anthropometric analysis were performed. This study demonstrated that triglycerides promote dysfunctions on HDL, increasing the cardiovascular risk. Blood pressure was higher in subjects with low HDL. Women presented higher levels of HDL-c and low percentage of fat mass. The highest levels of triglycerides were observed in older age. In addition, high levels of triglycerides were associated with higher total cholesterol and LDL-c levels, non-HDL-c, non-esterified fatty acids, and blood glucose, increasing in the ratio of non-HDL-c/HDL-c and ApoB/ApoA-I. The increase of triglycerides levels progressively impairs the antioxidant capacity of HDL, probably due to a higher occurrence of fatty acid peroxidation in individuals with hypertriglyceridemia. Patients with high HDL and low TG levels increased the Lag Time. Furthermore, a positive correlation was found between TG versus HDL particle size, variables that depend on age and anthropometric parameters.

Identifying the role of apolipoprotein A-I in prostate cancer / 亚洲男科学杂志(英文版)

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.

ERα promotes transcription of tumor suppressor gene / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Apolipoprotein A-I (ApoA-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 ApoA-I levels in various types of cancer, suggesting ApoA-I as a potential cancer biomarker. Herein, ectopically overexpressed ApoA-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 receptor α (ERα) signaling activates

Correlation between Pretreatment Serum Apolipoprotein Level and Prognosis of Small Cell Lung Cancer Patients / 中国肺癌杂志

BACKGROUND@#Lung cancer is the leading cause of cancer-related death, and small cell lung cancer (SCLC) has a poor prognosis in all types of lung cancer. This study evaluated the relationship between pretreatment serum apolipoprotein levels and prognosis in patients with SCLC, seeks a new index can guide diagnosis and treatment of SCLC.@*METHODS@#This study retrospectively analyzed the clinical data of 122 patients with SCLC. The clinical results of patients with serum apolipoprotein levels within 2 weeks before treatment were collected, including apolipoprotein AI (ApoA-I), apolipoprotein B (ApoB), and the ratio of apolipoprotein B to apolipoprotein AI (ApoB/ApoA-I). Patients' progression-free survival (PFS) and overall survival (OS) are the main outcome indicators. The best critical to determine the index's value by X-tile tool. For survival analysis, Kaplan-Meier method was used for analysis, and Cox regression analysis method was used for single factor analysis and multifactor analysis.@*RESULTS@#Compared with patients with low ApoA-I levels, patients with high ApoA-I levels (ApoA-I>1.12 g/L) had better OS (21.5 mon vs 12.3 mon, P=0.007) and PFS (7.3 mon vs 5.5 mon, P=0.017). In contrast, patients with higher ApoB/ApoA-I levels had worse median OS than patients with lower ApoB/ApoA-I levels (13.4 mon vs 20.7 mon, P=0.012). Multivariate Cox regression analysis showed that ApoA-I was an independent prognostic factor affecting PFS in SCLC patients (HR=0.67, 95%CI: 0.45-0.99, P=0.043). ApoB/ApoA-I is an independent risk factor for OS in patients with SCLC (HR=1.98, 95%CI: 1.21-3.23, P=0.007).@*CONCLUSIONS@#Serum ApoA-I level and ApoB/ApoA-I level before treatment can be important prognostic factors for SCLC, which is helpful to judge the prognosis of patients.

A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.

Correlation between ratio of Apo A1／Apo B and heart failure／ / 心血管康复医学杂志

To analyze the correlation between ratio of apolipoprotein A 1 (ApoA1 )／apolipoprotein B (ApoB) and heart failure (HF).Methods : A total of 150 HF patients treated in our department were divided into NYHA class II group (n＝54) ,class III group (n＝48) and class IV group (n＝48).Their LVEF ,stroke volume (SV) ,cardiac output (CO) ,cardiac index (CI) ,levels of BNP ,serum Apo A1 and Apo B were measured ,and Apo A1／Apo B was calculated ,then correlation analysis was performed .Results : Compared with class II group ,there were significant reductions in LVEF [ (37. 29 ± 6. 25)% vs.(34. 66 ± 5.90)% vs.(32.55 ± 5. 23)%] ,SV [ (36. 40 ± 4.18) ml vs .(34.05 ± 3. 49) ml vs.(31.72 ± 5.44) ml] ,CO [ (3.71 ± 0.59) L／min vs .(3.39 ± 0. 43) L／min vs.(3. 17 ± 0.44) L／min] ,CI [ (2. 16 ± 0.50 ) L· min－1 · m－2 vs.(1. 76 ± 0.37 ) L· min－1 · m－2 vs.(1. 44 ± 0.43) L·min－1 ·m－2 ] ,and ApoA1／ApoB [ (1.17 ± 0.44) vs.(0. 98 ± 0.28) vs.(0. 65 ± 0.24)] in class III group and class IV group ,and those of class IV group were significantly lower than those of class III group ;significant rise in levels of plasma BNP [ (469.23 ± 63. 12) pg／ml vs.(612. 52 ± 80.34) pg／ml vs.(822.96 ± 97.22) pg／ml] in class III group and class IV group ,and those of class IV group were significantly higher than those of class III group ,P＜0.05 or ＜0.01. Pearson correlation analysis indicated that serum Apo A 1／Apo B was significant positively correla‐ted with LVEF ,SV ,CO and CI ( r＝0. 422～0. 603 , P＜0.05 or ＜0.01) ,and significant inversely correlated with plasma BNP level ( r＝ －0. 625 , P＝0.002).Conclusion :The worse the cardiac function is ,the lower serum Apo A1／Apo B is in HF patients .There is positive correlation between them .21－3

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.

Research progress in small molecule drugs based on high-density lipoprotein for anti-atherosclerosis / 药学学报

A large number of epidemiological data have shown that the high-density lipoprotein cholesterol level is negatively related to atherosclerotic cardiovascular disease, suggesting that high-density lipoprotein may have the effect of anti-atherosclerosis. It may play the role of anti-atherosclerosis, through the promotion of cholesterol reverse transport, anti-inflammatory, antioxidant, and against thrombosis and fibrinolysis and so on. Among them, reverse cholesterol transport which is mainly regulated by apolipoprotein A-I, ATP-binding cassette transporter 1, liver X receptor and cholesteryl ester transfer protein, may play a major role in the maintenance of cholesterol homeostasis and reversing the course of atherosclerosis. These regulatory factors may be potential targets in high density lipoprotein-based drug discovery. In this review, these key proteins are discussed for the current status of small molecule drugs against atherosclerosis.

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 .

Apolipoprotein A1 localization in sperms and its antibody′s effect on human sperm function / 中华检验医学杂志

Objective To investigate the presence of apolipoprotein A 1 (APOA1) and its function in human spermatozoa. Methods The expression assays for APOA 1 were carried out by immunofluorescence and Western blotting in human sperm cells . Set up a blank control group , rabbit polyclonal IgG group , which contain anti-APOA1 antibody 10 μg/ml, 20 μg/ml and 40 μg/ml, to treat normal semen samples and incubated at 37 ℃for 1 h, 2 h and 3 h.The progressive motility of spermatozoa was determined bya computer-assisted motion analyzer ( CASA ) , apoptosis rate by flow cytometry and ultrastructural changes by electron microscopy .Comparisons of sperm progressive motility and apoptosis rate were performed by independent sample t tests.Results The study showed APOA1 protein mainly located in the sperm head , the molecular size was 31000.A significant decline in sperm progressive motility was observed after 1,2 and 3 hours of incubation with APOA1 antibody.There was a statistically significant difference between the blank control group and the APOA 1 antibody concentration of 20 μg/ml and 40 μg/ml groups [ 1 hour after incubation , blank control group ( 68.65％ ±15.70％) with 20 μg/ml group (48.45％±5.20％), 40 μg/ml group(39.25％±7.89％), t=2.442, 3.345 , both P<0.05;2 hours after incubation, blank control group(55.33％±10.12％) with 20 μg/ml group(28.68％±11.70％), 40μg/ml group(18.13％ ±10.52％), t=3.445, 5.097,both P<0.05; 3 hours after incubation, blank control group(35.73％±14.08％) with 20μg/ml group(15.53％±8.42％), 40μg/ml group(9.98％± 7.08％), t=2.462, 3.268,both P<0.05].After incubation 2 hours, the percentage of apoptotic cells increased from 16.02％ ±4.28％ in the blank control group to 21.72％ ±2.67％ ( 20 μg/ml APOA1 antibody)and 28.01％±3.93％(40 μg/ml APOA1 antibody), respectively (t=3.177, 5.834, both P<0.01).Treatment with 40 μg/ml APOA1 antibody for 4 hours resulted in major morphological changes to sperm cells observed by electron microscope , including membrane distension ,vacuole formation and different periods of apoptosis cells .Conclusion APOA1 plays an important role in maintaining sperm motility and survival rate,however the mechanism needs further study .

Effect of epigallocatechin-3 gallate on cholesterol efflux in foam cells and its mechanism / 中华老年心脑血管病杂志

Objective To study the effect of epigallocatechin-3 gallate (EGCG) on cholesterol efflux in foam cells and its mechanism.Methods THP-1 cells were induced to differentiate into macrophages which were then transformed to foam cells.Foam cells were divided into 0 μmol/L EGCG group,10 μmol/L EGCG group,30 μmol/L EGCG group,and 100 μmol/L EGCG group (1.5 × 106 in each group).Their cholesterol content was measured with a cholesterol test kit,apoA-I-mediated cholesterol efflux was assayed with a liquid scintillation counter,expression of ATP-binding cassette A1 (ABCA1) was detected by RT-PCR and Western blot respectively.Results The ABCA1 mRNA and protein expression levels and cholesterol efflux were significantly higher while the cholesterol content was significantly lower in 10 μmol/L EGCG group,30 μmol/L EGCG group,and 100 μmol/L EGCG group than in 0 μmol/L EGCG group (7.04％ ±0.21％,7.75％±0.17％ and 8.53％±0.18％ vs 3.37％±0.16％,P＜0.01;419.33±19.75 mg/g,352.58± 14.23 mg/g and 312.62±17.45 mg/g vs 520.51 ±20.62 mg/g,P＜0.01),and in 30 μmol/L EGCG group,100μmol/L EGCG group than in 10μmol/L EGCG group (P＜0.05).Conclusion EGCG increases cholesterol efflux and decreases cholesterol content in foam cells by upregulating the transcription and expression of ABCA1.

The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia / O efeito do extrato de semente de uva vermelha na atividade do soro paraoxonase em doentes com hiperlipidemia leve a moderada

ABSTRACT: CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

RESUMO: CONTEXTO E OBJETIVO: Extrato de semente de uva vermelha (RGSE) contém complexos de proantocianidinas oligoméricas como classe de flavonoides. Estes compostos são antioxidantes potentes e exercem muitos efeitos de promoção da saúde. Este estudo visou determinar os efeitos de RGSE nos níveis séricos de triglicérides (TG), colesterol total (TC), colesterol de lipoproteína alta-densidade (HDL-C), colesterol de lipoproteína baixa-densidade (LDL-C), apolipoproteína AI (apo-AI) e atividade de paraoxonase (PON) em pacientes com hiperlipidemia leve a moderada (MMH). DESENHO E LOCAL: Estudo clínico randomizado duplo-cego controlado com placebo, realizado no Hospital Shahid-Modarres (Teerã, Irã) e na Universidade de Ciências Médicas de Tabriz. Setenta pacientes com MMH foram aleatoriamente designados para receber tratamento (200 mg/dia de RGSE) ou placebo durante oito semanas. RESULTADOS: Elevação significativa nos níveis séricos de apo-AI (P = 0,001), HDL-C (P = 0,001) e atividade de PON (P = 0,001) e diminuição marcada nas concentrações de TC (P = 0,015), TG (P = 0,011) e LDL-C (P = 0,014) foram encontradas nos casos. Atividade de PON mostrou correlação significativa com apo-AI (r = 0,270; P < 0,01) e HDL-C (r = 0,45; P < 0,001). Diferenças significativas entre os grupos RGSE e controle (antes e após tratamento) para TC (P = 0,001), TG (P = 0,001), PON (P = 0,03), apo-AI (P = 0,001) e LDL-C (P = 0,002) foram observadas. CONCLUSÃO: É possível que RGSE aumente atividade de PON principalmente através da elevação dos níveis de HDL-C e apo-AI em pacientes MMH. Ele pode, assim, ter efeitos benéficos potenciais na prevenção de estresse oxidativo e aterosclerose nesses pacientes.

E17110 promotes reverse cholesterol transport with liver X receptor β agonist activity in vitro

Liver X receptor (LXR) plays an important role in reverse cholesterol transport (RCT), and activation of LXR could reduce atherosclerosis. In the present study we used a cell-based screening method to identify new potential LXRβ agonists. A novel benzofuran-2-carboxylate derivative was identified with LXRβ agonist activity: E17110 showed a significant activation effect on LXRβ with an EC50 value of 0.72 μmol/L. E17110 also increased the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 macrophages. Moreover, E17110 significantly reduced cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages. Interestingly, we found that the key amino acids in the LXRβ ligand-binding domain had distinct interactions with E17110 as compared to TO901317. These results suggest that E17110 was identified as a novel compound with LXRβ agonist activity in vitro via screening, and could be developed as a potential anti-atherosclerotic lead compound.

Age-Dependent Effect of Cyclic Feeding Regimen on the Level of Serum Apolipoproteins in Young and Old Rats.

the aim of this study was to investigate the influence of intermittent fasting (IF) on the content of blood serum apolipoproteins in young and old animals and to ascertain whether there exist adaptation mechanisms to this dietary regimen. Study design: young (3-month) and old (20-month) rats were individually housed and randomly assigned to one of five groups (with 10 rats per group): (AL) - fed ad libitum; (IF1) - provided access to a limited amount of food (4g/100g and 2g/100g of food/body weight for young and old rats, respectively) every other day for 10 days; (R1) - refeeded ad libitum for 20 days after IF1; (IF2) - provided the same regimen as for IF1, but after successive IF1 and R1; (R2) - refeeded ad libitum for 10 days after IF2. Methodology: plasma proteins were separated by one dimensional SDS-PAGE using a 7.5-15% gradient separating gel. Results: IF1 with 30% weight loss resulted in ~28% and ~24% decrease and ~121% increase in serum apolipoprotein A-I (apoA-I), apolipoprotein B-100 (apoB-100), and apolipoprotein E (apoE) levels of young rats, respectively, and after R1 the level of these proteins was characterized by ~37%, ~66%, ~22% increase in comparison with control. IF1 and R1 in old animals were followed by ~53% increase in apoE content and ~13% decrease in the amount of apoB. IF2 was coupled with ~32% decrease in apoA-I level and ~133% increase in apoE concentration in young animals and ~39% and ~38% decrease in apoA-I and apoB-100 level in old animals, respectively. R2 produced ~48% and ~49% increase in apoA-I and apoE levels of young rats, respectively, and to ~31% increase in apoA-I content of old rats. Conclusion: the main outcome reached is the identification of differences in the effects of the dietary regimen during reapplication on apoE and apoB-100 serum levels in old animals and on apoA-I level in the case of young animals.

Activity of Lecithin Cholesterol Acyl Transferase and Apolipoprotein A-I in Newly Detected Type 2 Diabetes mellitus.

Aims: 1. To study the levels of Apolipoprotein A-I and activity of Lecithin cholesterol acyl transferase (LCAT) in newly detected type 2 Diabetes Mellitus. Study Design: Cross sectional study. Place and Duration of Study: Department of Biochemistry and Department of Medicine, Belgaum Institute of Medical Sciences (BIMS), Belgaum, Karnataka, India, between November 2011 and June 2013. Methods: Study included 100 patients (50 men, 50 women, age range 30-60 years) with newly detected type 2 Diabetes Mellitus and 100 age and sex matched healthy participants. LCAT activity was assessed by measuring the difference between esterified and free cholesterol. Determination of free and esterified cholesterol was done by using digitonin precipitation method. Apolipoprotein A-I was measured by immunoturbidemetric method using semi auto analyzer. HDL cholesterol level was measured by CHOD-POD method. Results: The mean±SD value of various parameters in newly detected type 2 Diabetes Mellitus was HDL cholesterol(33.37±4.44mg/dl), Apolipoprotein A-I(133.10±24.22mg/dl), and LCAT activity(59±9.86 IU/L), versus HDL cholesterol(48.76±16.84mg/dl), Apolipoprotein A-I(188.72±19.49mg/dl) and LCAT activity (91.74±6.50IU/L) in controls. LCAT activity, Apolipoprotein A-I and HDL levels were significantly (p < 0.01) decreased in patients with newly detected type 2 Diabetes Mellitus when compared with healthy participants. Conclusion: The reduced LCAT activity, Apolipoprotein-A-I and HDL cholesterol may be associated with a reduction in Reverse cholesterol transport(RCT) and contribute to the development of atherosclerosis in newly detected type 2 Diabetes Mellitus.

Papel protector de las lipoproteínas de alta densidad en sepsis: aspectos básicos e implicancias clínicas / Protective role of high density lipoproteins in sepsis: basic issues and clinical implications

High density lipoproteins (HDL) are responsible of reverse cholesterol transport and play an important antiatherogenic role. In recent years, several studies suggest that HDL have additional functions, including a possible anti-inflammatory activity in infectious conditions. Furthermore, available evidence indicates that the presence of lipopolysaccharide (LPS) within the circulation during infectious states induced by gram-negative bacteria may be involved in the decrease in HDL cholesterol levels and changes in lipoprotein composition, which have been associated with a higher mortality due to sepsis in animal models and in humans. In this article, we review this subject and also discuss possible mechanisms that explain the positive impact achieved by native HDL, reconstituted HDL, or HDL apolipoprotein peptides on the inflammatory response and mortality in models of endotoxemia. In this regard, it has been proposed that one of the mechanisms by which HDL protect against sepsis may be mediated by its binding ability and/or neutralizing capacity on LPS, avoiding an excessive response of the immune system. Thus, increasing blood levels of HDL and/or parenteral HDL administration may represent a new anti-inflammatory tool for managing septic states in humans.

Las lipoproteínas de alta densidad (HDL) son responsables del transporte reverso de colesterol y ejercen un importante papel anti-aterogénico. En los últimos años, diversos estudios indican que las HDL también tendrían otras funciones críticas, incluyendo una posible actividad anti-inflamatoria durante estados infecciosos. Además, la evidencia disponible sugiere que la presencia de lipopolisacárido (LPS) en la circulación durante estados infecciosos inducidos por bacterias gramnegativas podría estar involucrado en la disminución del colesterol HDL y los cambios en composición de esta clase lipoproteínas, lo cual se asociaría con una mayor tasa de mortalidad por sepsis en modelos animales y en humanos. En este trabajo, se revisan los antecedentes mencionados y además se discuten posibles mecanismos que explican la disminución de la respuesta inflamatoria y de la mortalidad que se logran en modelos de endotoxemia tratados con HDL o preparaciones similares. En este sentido, se ha propuesto que uno de los mecanismos protectores de las HDL estaría mediado por su capacidad de unión y/o neutralización del LPS, evitando una respuesta exacerbada del sistema inmune. De esta manera, el aumento de los niveles sanguíneos de HDL y/o su administración parenteral podrían constituir nuevas herramientas anti-inflamatorias para el manejo de estados sépticos en humanos.

Inhibitory effect of apolipoprotein A-I mimetic peptide D-4 F on scavenger receptor A1 in macrophage-derived foam cells / 中国病理生理杂志

AIM:To investigate the inhibitory effect of apolipoprotein A-I mimetic peptide D-4F on the scaven-ger receptor A1 ( SR-A1 ) in macrophage-derived foam cells induced by oxidized low-density lipoprotein ( ox-LDL ) . METHODS:RAW264.7 cells were pretreated with different concentrations (12.5, 25 and 50 mg/L) of D-4F or 50 mg/L inactive control peptide scrambled D-4F (sD-4F) for 1 h or endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyr-ic acid (5 mmol/L) for 30 min, followed by the treatment with 100 mg/L ox-LDL for 12 h.In addition, the cells were pre-treated with 50 mg/L D-4F or sD-4F for 1 h, and then stimulated with 2 mg/L tunicamycin (TM;an ERS inducer), for 4 h.The viability of the cells was measured by MTT assay, and the content of intracellular total cholesterol ( TC) was meas-ured by a tissue/cell TC assay.The protein and mRNA levels of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blotting and quantitative real-time PCR, respectively.The fluorescence intensity of DiI-ox-LDL in the cells was detected by a multifunctional microplate reader.RESULTS:D-4F significantly reduced ox-LDL-induced macro-phage injury and intracellular cholesterol accumulation, and attenuated the ox-LDL-induced expression of SRA1 and GRP78 in a dose-dependent manner.Additionally, D-4F significantly inhibited the TM-induced protein expression of SR-A1 and GRP78, and attenuated the uptake of ox-LDL by macrophages.CONCLUSION: D-4F reduces ox-LDL-induced macro-phage cholesterol accumulation and injury by inhibiting SR-A1 expression.The mechanism may be related to the inhibition of ERS signaling pathway mediated by GRP78.

Study Progress in Apolipoprotein A-I's Gene Polymorphism and Its Relationship with Reverse Cholesterol Transport / 世界科学技术-中医药现代化

Apolipoprotein A-I (apoA-I) is a member of the apolipoprotein A family, which was discovered the earli-est. It has an important role in the regulation of lipid metabolism, which mainly includes cholesterol synthesis and transfer. Therefore, apoA-I is closely related to hyperlipidemia and atherosclerosis. Clinically, serum ApoA-I/ApoB has been used as one of the indexes of hyperlipidemia. This article reviewed the study progress in ApoA-I's gene polymorphism and its relationship with reverse cholesterol transport (RCT).

Levels of apolipoproteins as risk factors for coronary artery disease / Níveis de apolipoproteínas como fatores de risco para doença arterial coronariana

INTRODUCTION: The Saudi population is renowned for their unhealthy diet and physical inactivity. OBJECTIVE:To investigate apolipoproteins B (apo B), A-I (apo A-I) and B/A-I as risk factors that might be associated with increased incidence of the coronary artery disease. METHODS: Two hundred and twenty subjects suspected of having the coronary artery disease underwent coronary angiography and blood draw following a 12-hour fast. Apolipoproteins B and A-I were both measured by turbidimetric methods. RESULTS: One hundred and forty subjects were positive and 80 subjects were negative for the coronary artery disease. Both apolipoproteins were found to be statistically significant as risk factors for the coronary artery disease: apolipoprotein B (105.33±29.22 versus 94.56±24.35 mg/dL, p<0.003), apolipoprotein A-I (123.98±25.6 versus 133.5±24.1 mg/dL, p<0.004) and apolipoproteins B/A-I (0.88±0.28 versus 0.72±0.2, p<0.0001). CONCLUSIONS:Measurements of apolipoproteins B, A-I and calculation of apolipoproteins B/A-I ratio either instead of or in addition to the customary measurements of lipoprotein cholesterol may significantly add to predicting and assessing the coronary risk factors in the Saudi population.

INTRODUÇÃO: A população da Arábia Saudita é conhecida por sua dieta não-saudável e inatividade física. OBJETIVO: Investigar as apolipoproteínas B (apo B), AI (apo AI) e B/AI como fatores de risco que podem estar associados ao aumento da incidência da doença arterial coronariana. MÉTODOS: Duzentos e vinte pacientes com suspeita de doença art RESULTADOS: Cenerial coronariana foram submetidos à angiografia coronária e extração de sangue após jejum de 12 horas. As apolipoproteínas B e AI foram medidas por métodos turbidímetros.to e quarenta pacientes foram positivos e 80 foram negativos para a doença arterial coronariana. Ambas apolipoproteínas foram estatisticamente significativas como fatores de risco para doença arterial coronariana: apolipoproteínas B (105,33±29,22 versus 94,56±24,35 mg/dL, p<0,003), AI (123,98±25,6 versus 133,5±24,1, p<0,004) e B/A-I (0,88±0,28 versus 0,72±0,2, p<0,0001). CONCLUSÕES: As medidas das apolipoproteínas B, AI e o cálculo da relação B/AI tanto por ou em adição às medidas habituais de colesterol das lipoproteínas podem aumentar significativamente a previsão e avaliação dos fatores de risco coronariano na população saudita.

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.