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.

Advances in ApoA- I mimic peptides against atherosclerosis / 中国药理学通报

Apolipoprotein A-I (ApoA-I), the main protein component of high density lipoprotein (HDL) , which plays a key role in the process of reverse cholesterol transport (RCT) , is considered as an important anti-atherosclerosis (As) drug target. ApoA- I mimic peptides developed based on its a-helix, and HDL mimic peptides that developed by recombinant ApoA- I have entered clinical trials, exhibiting favorable RCT promotion and anli-As activity. The paper reviewed the advances in the structure and function of ApoA- I , the molecular interaction mechanism between ApoA-1 and ABCA1 ( ATP-binding cassette transporter Al) , LCAT (lecithin cholesterol acyl transferase) and SR-B1 (scavenger receptor class B type 1) , and anti- As activity of ApoA- I mimic peptides, which would provide references for anli-As new drug development based on ApoA- I mimic peptides.

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

Association of HDL-Cholesterol Level and ApoB/ApoA Ratio with Coronary Artery Disease Severity and Type 2 Diabetes Mellitus.

The ApoB/ApoA-I ratio reflects the balance between pro- and anti-atherogenic particles, all of which contain cholesterol. The ApoB/A ratio is valid in both genders of all ages and is independent of the lipid levels and phenotypes. This study has been designed to investigate the association between the ratio of apolipoprotein B (apo B)/ apolipoprotein A1 (apo A1) and HDL-C with severity of coronary artery disease in patients with and without type 2 diabetes mellitus.METHODSThe present case control study was carried out in departments of Cardiology and Biochemistry, Vinayaka Missions Hospital, Salem. Fasting blood samples have been collected from 109 CAD patients and 71 control subjects. Serum lipids were measured enzymatically, ApoA-I and Apo B were analysed by immunoturbidimetric method. The study was approved by ethics committee and informed consent was obtained.RESULTSIn our study, Apo A-1 level was significantly low (1.187±0.20) and Apo B was found to be significantly high (1.64±0.62) in CAD with diabetes subjects, when compared to CAD without diabetes. HDL level was found to be significantly lowered in CAD patients. A significant positive association was observed between ApoA-1 and lipid parameters in CAD subjects with HDL-C at (p= 0.00).CONCLUSIONSApo B/Apo A1 ratio may be a healthier forecaster than conventional lipid markers to explore the severity of CAD. This study suggests that instead of measurement of lipid profiles alone, a better indicator apo B, A-I and B/A-I ratio measurement, which in turn highlights the cholesterol balance, can reduce the delay in the recognition of CAD.

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 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.

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.

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

Expression analysis of apolipoproteins AI & AIV in hepatocellular carcinoma: A protein-based hepatocellular carcinoma-associated study

Background & objectives: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. The objective of this study was to find out the differential expression of apolipoproteins (ApoAI and ApoAIV) in HCC and cases of liver cirrhosis and chronic hepatitis (controls) without HCC and to compare ApoAI and ApoAIV expression with alpha-foetoprotein (AFP), the conventional marker in HCC. Methods: Fifty patients with HCC and 50 controls comprising patients with liver cirrhosis (n=25) and chronic hepatitis (n=25) without HCC were included in this study. Total proteins were precipitated using acetone precipitation method followed by albumin and IgG depletion of precipitated protein using depletion kit. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expression changes of ApoAI and ApoAIV were confirmed by western blotting using specific primary and secondary polyclonal antibodies followed by densitometric protein semi-quantitative estimation. ApoAI, ApoAIV and AFP were measured in the plasma samples by ELISA method. Results: Semi-quantitative densitometric image analysis of the western blot images and the comparison between HCC patients with those without HCC (control) revealed differential expression of ApoAI and ApoAIV. Levels of ApoAI were significantly higher in patients with HCC compared to controls without HCC (0.279�216 vs 0.171�091 and 0.199�014; P <0.001). Levels of ApoAIV were significantly lower in patients of HCC compared to controls without HCC (0.119�061 vs 0.208�07 and 0.171�16; P <0.01). ELISA assays of apolipoproteins (ApoAI and ApoAIV) revealed similar results of expression of ApoAI and ApoAIV as detected in western blotting densitometric image analysis. Interpretation & conclusions: Increased expression of ApoAI and decreased expression of ApoAIV in HCC patients compared to controls without HCC revealed the abnormalities in HCC. These molecules need to be studied further for their use as potential biomarkers in the future diagnostic tools along with other conventional biomarkers for screening of HCC cases. It needs further analysis in higher number of patient population.

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 .

Correlation of apolipoprotein AI, apolipoprotein B and their ratio with the severity of cerebral white matter lesions / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the correlation of apolipoprotein AI (ApoAI), ApoB, ApoB/ApoAI and the severity of brain white matter lesions (WML).</p><p><b>METHODS</b>A total of 648 patients with WML confirmed by brain magnetic resonance imaging (MRI) were divided into mild WML group (=386) and moderate to severe WML group (=262) according to evaluations with the Fazekas scale. The demographic data, blood biochemical parameters and the levels of ApoAI, ApoB and ApoB/AI ratio were compared between the two groups to identify the risk factors of moderate to severe WML.</p><p><b>RESULTS</b>Univariate analysis showed that age, gender, hypertension, diabetes, coronary heart disease, previous stroke, homocysteine, HDL-C, ApoAI, and ApoB/AI ratio all differed significantly between the two groups ( < 0.05), but ApoB levels were similar between them ( > 0.05). Multivariate logistic regression analysis revealed that with ApoAI and ApoB/AI ratio as the continuous variables, after adjustment for the compounding factors, ApoB/AI ratio was an independent risk factor (OR=11.456, 95% : 3.622-36.229, < 0.001) and ApoAI was an independent protective factor for moderate to severe WML (OR=0.068, 95% : 0.018-0.262, < 0.001). With the upper quartiles of ApoAI level (1.38 g/L) and ApoB/AI ratio (0.58) as their respective cutoff values, patients with a high ApoAI level and a low ApoB/AI ratio were found to have the lowest incidence of moderate to severe WML ( < 0.001).</p><p><b>CONCLUSIONS</b>An increased ApoB/AI ratio is an independent risk factor and an increased ApoAI level is an independent protective factor for moderate to severe WML.</p>

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.

Effect of Apolipoprotein AI on MCP?1 Plasma Levels,Monocyte Subset Proportions,and in Vitro CCR2 Expression / 中国医科大学学报

Objective To explore effects of apoAI on MCP?1 levels in the plasma and the Ly6Chi monocyte proportion in the blood and spleen of atherosclerotic mice,as well as on CCR2 expression in vitro. Methods Sixteen male apoE?/?mice were fed with high cholesterol diet for 12 weeks. Mice were randomly divided into control and apoAI groups and were administered with PBS or apoAI(40 mg/kg),respectively,via tail vein on the 1st and 3rd day before sacrifice. Mice in both groups were administered LPS(25μg/mouse)via intraperitoneal injection 12 h before sacrifice. Plas?ma levels of MCP?1 were determined using ELISA,and the Ly6Chi monocyte proportion was analyzed using flow cytometry. In addition,human monocytic THP?1 cells were randomly divided into control and apoAI(10 mg/L)?treated groups,pretreated with corresponding intervention,and incubated with LPS(10μg/L). CCR2 expression levels were measured by Western blotting. Results Compared with the control treatment, apoAI treatment remarkably reduced MCP?1 levels in plasma and Ly6Chi monocyte proportion in the blood and spleen(P<0.01). Furthermore, apoAI treatment inhibited CCR2 expression in monocytes in vitro(P<0.05). Conclusion apoAI can reduce MCP?1 levels in plasma and the Ly6Chi monocyte proportion in the blood and spleen and can inhibit CCR2 expression in monocytes in vitro.

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.