Apolipoprotein (apo) C-III is a small protein (79 amino acids) and a component of triacylglycerol (TAG)-rich very low density lipoproteins (VLDL) and high density lipoproteins. We have unraveled a new intracellular role of apoCIII in promoting hepatic VLDL(1) (Sf>> 100) assembly/secretion under lipid-rich conditions. Feeding apoc3-null mice with a high fat diet for two weeks or palm oil gavage failed to stimulate VLDL(1) production in vivo. Reconstitution of apoC-III expression using adenovirus encoding human apoC-III resulted in robust production of VLDL(1) containing apoB-100 or apoB-48. The stimulatory effect of human apoC-III on the assembly and secretion of VLDL(1) was recapitulated ex vivo in McA-RH7777 cells cultured in lipid-rich media. Metabolic labeling experiments showed that apoC-III plays a central role in (i) the formation of lumenal lipid droplets (LLD) rich in TAG, and (ii) promoting bulk TAG incorporation during VLDL(1) assembly. Structure-function analysis of naturally occurring apoC-III variants (Ala23Thr and Lys58Glu) defined two functional domains that play respective roles in LLD formation and VLDL(1) assembly. Unraveling the intracellular role of apoC-III in the atherogenic TAG-rich VLDL(1) production provides new insights into the strong influence of the APOA5-A4-C3-A1 gene locus on plasma TAG concentrations and premature atherosclerosis.

The inhibition of low-density lipoprotein (LDL) oxidation by high-density lipoprotein (HDL) is a major antiatherogenic property of this lipoprotein. This activity is due, in part, to HDL associated proteins. However, whether these proteins interact in the antioxidant activity of HDL is unknown. LDL was incubated with apolipoprotein A1 (apo A1), lecithin:cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON1) alone or in combination, in the presence or absence of HDL under oxidizing conditions. LDL lipid peroxide concentrations were determined. Apo A1, LCAT, and PON1 all inhibit LDL oxidation in the absence of HDL and enhance the ability of HDL to inhibit LDL oxidation. Their effect was additive rather than synergistic; the combination of these proteins significantly enhanced the length of time LDL was protected from oxidation. This seemed to be due to the ability of PON1 to prevent the oxidative inactivation of LCAT. Apo A1, LCAT, and PON1 can all contribute to the antioxidant activity of HDL in vitro. The combination of apo A1, LCAT, and PON1 prolongs the time that HDL can prevent LDL oxidation, due, at least in part, to the prevention LCAT inactivation.

Serum cholesterol, HDL cholesterol (HDL-C), and apoproteins, A1, A2 and B were determined in 70 male survivors of myocardial infarction and in an equal number of healthy controls, matched for age, sex and body mass index. In univariate analyses, the Apo B/Apo A1 ratio discriminated the best between cases and controls, giving a 72% exact classification. In a multivariate analysis, the Apo B/Apo A1 ratio, HDL-C and the Apo A2/Apo A1 ratio contributed independently to the discrimination of cases from controls while the overall exact classification was 82%. These promising results were comparable in younger and older subgroups. Thus, the determination of apoproteins yielded complementary information in this cross-sectional survey and warrants further study in a prospective setting.

BACKGROUND

Recent genome-wide association (GWA) studies have identified a number of novel genetic determinants of blood lipid concentrations in Europeans. However, it is still unclear whether these loci identified in the Caucasian GWA studies also exert the same effect on lipid concentrations in the Chinese population.

RESULTS

We conducted a replication study assessing associations between SNPs at 15 loci and blood lipid and lipoprotein concentrations in two Chinese cohorts, comprising 2533 and 2105 individuals respectively. SNPs in APO(A1/C3/A4/A5), TIMD4-HAVCR1, DOCK7, TRIB1, ABCA1, and TOMM40-APOE showed strong associations with at least one lipids trait, and rs174546 in FADS1/2/3 showed modest association with triglyceride in the Chinese population.

CONCLUSIONS

We successfully replicated 7 loci associated plasma lipid concentrations in the Chinese population. Our study confirmed the implication of APO(A1/C3/A4/A5), TOMM40-APOE, ABCA1, DOCK7, TIMD4-HAVCR1, TRIB1 and FADS1/2 in plasma lipid and lipoprotein concentrations in Chinese population.

Although several studies have shown that asymptomatic human immunodeficiency virus infection elicits an increase in whole body protein turnover, it is not known whether this increased protein turnover includes changes in the kinetics of acute-phase proteins (APPs). To answer this question, we measured 1) the plasma concentrations of four positive (C-reactive protein, alpha1-antitrypsin, haptoglobin, and fibrinogen) and four negative APPs [albumin, high-density lipoprotein (HDL)-apolipoprotein (apo) A1, transthyretin, and retinol-binding protein] and 2) the fractional (FSR) and absolute (ASRs) synthesis rates of three positive and three negative APPs using a constant intravenous infusion of [2H5]phenylalanine in five subjects with symptom-free acquired immunodeficiency syndrome (AIDS) and five noninfected control subjects. Compared with the values of the controls, the plasma concentrations, FSRs, and ASRs of most positive APPs were higher in the AIDS group. The negative APPs had faster FSRs in the AIDS group, there was no difference between the ASRs of the two groups, and only HDL-apoA1 had a lower plasma concentration. These results suggest that symptom-free AIDS elicits an APP response that is different from bacterial infections, as the higher concentrations and faster rates of synthesis of the positive APPs are not accompanied by lower concentrations and slower rates of synthesis of most of the negative APPs.

OBJECTIVE

The ATP-binding cassette transporter A1 (ABCA1) is essential protein involved in lipid metabolism. The present study was undertaken to detect the possible association of polymorphisms in the ABCA1 gene [rs2230806 (R219K) and rs2230808 (R1587K)] and lipid profile in Greek young nurses.

METHODS

The study population consisted of 308 unrelated nurses who were genotyped and the ABCA1 polymorphisms were detected. Additionally, lipid profile [total cholesterol (TC), triglycerides (TGs), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) A] was evaluated.

RESULTS

There was no difference in the genotypic and allelic frequencies of the R219K polymorphism according to lipid profile. The R1587K genotypes differed significantly according to TC, LDL-C and TGs concentration (p = 0.023, p = 0.014 and p = 0.047, respectively). Particularly, significant difference in TC, LDL-C and TGs concentration was detected between RK and RR genotypes (p = 0.006, p = 0.004, p = 0.014, respectively). Women with RK genotype compared to RR genotype had higher concentration of TGs (134.25 mg/dl vs 108.89 mg/dl, p = 0.014, respectively), total cholesterol (207.41 mg/dl vs 187.69 mg/dl, p = 0.006, respectively), and LDL-C (110.6 mg/dl vs 96.9 mg/dl, p = 0.004, respectively).

CONCLUSIONS

These findings suggest that the R1587K polymorphism of ABCA1 gene was associated with lipid profile of Greek nurses. Women with RK genotype had higher TGs, total and LDL-C concentration compared to RR genotype. These observations may be significant in assessing the risk of CAD since a 1% change in LDL-C is associated with a 1% change of cardiovascular events. Also, TGs concentration were documented to play a significant role in women. However, this needs to be confirmed by larger studies.

Isoorientin (ISO), a natural flavonoid, has been found to have multiple biological properties. In the present study, obese mice with high-fructose (HF)-induced liver injury were used to investigate the hepatoprotective effects of ISO. The results showed that ISO significantly reduced the serum lipid parameters in mice fed 20% HF water. Meanwhile, ISO appeared to alleviate HF-induced lipid metabolic disorders by increasing the serum levels of apo-A1 and decreasing the serum apoB levels, apoB/apo-A1 ratio, and FAS activity in the liver. ISO also remarkably ameliorated HF-induced hepatic oxidative injury and inflammation by decreasing ALT, AST, and ALP levels; enhancing antioxidant enzyme activities; and inhibiting inflammatory cytokine (TNF-α, IL-1, IL-6) release. Histopathology of liver stained by H&E and Oil Red O showed the liver steatosis and oxidative injury after HF treatment and the protective effect of ISO. Furthermore, aortic pathology observation found that ISO had a protective effect on the vascular endothelium. This is the first report that ISO efficiently inhibited HF-induced hyperlipidemia and liver injury by ameliorating lipid metabolism, enhancing the antioxidant defensedefense system, and regulating the secretion of inflammatory cytokines.

BACKGROUND

Ginsenoside Rp1 (G-Rp1) is a novel ginsenoside derived from ginsenoside Rk1. This compound was reported to have anticancer, anti-platelet, and anti-inflammatory activities. In this study, we examined the molecular target of the antiproliferative and proapoptotic activities of G-Rp1.

METHODS

To examine the effects of G-Rp1, cell proliferation assays, propidium iodine staining, proteomic analysis by two-dimensional gel electrophoresis, immunoblotting analysis, and a knockdown strategy were used.

RESULTS

G-Rp1 dose-dependently suppressed the proliferation of colorectal cancer LoVo cells and increased their apoptosis. G-Rp1 markedly upregulated the protein level of apolipoprotein (Apo)-A1 in LoVo, SNU-407, DLD-1, SNU-638, AGS, KPL-4, and SK-BR-3 cells. The knockdown of Apo-A1 by its small-interfering RNA increased the levels of cleaved poly(ADP-ribose) polymerase and p53 and diminished the proliferation of LoVo cells.

CONCLUSIONS

These results suggest that G-Rp1 may act as an anticancer agent by strongly inhibiting cell proliferation and enhancing apoptosis through upregulation of Apo-A1.

Human Lp[a] was isolated in preparative amounts from two donors; the native lipoprotein and its constituent apoproteins, apo[a] and apoB, were characterized extensively. Based on differences in apparent molecular weight, four different isoforms of apo[a], a1-a4, were observed between the two donors. The number and relative distribution of these isoforms varied between donors but were constant for each donor. Each apo[a] isoform was shown to be derived from a discrete apo[a]-B100 disulfide-linked complex present before reduction. Complete delipidation of Lp[a] was followed by solubilization, reduction, and carboxamidomethylation of the constituent apoproteins. These apoproteins were then separated by immunoaffinity chromatography using anti-apo[a]- or anti-apoB-Sepharose; their purity and structural integrity were demonstrated by Western blot analysis. ApoB isolated by this procedure was essentially identical to apoB from autologous LDL with respect to molecular weight, secondary structure, amino acid composition, and sialic acid content. However, apo[a] differed from apoB in that it exhibited: a much less alpha-helical, less beta, but much more disordered structure; a lower proportion of aspartate, isoleucine, leucine, phenylalanine, and lysine, but a higher proportion of proline, glycine, and threonine; and a much higher content of sialic acid. These results indicate that apo[a] is not a superglycosylated form of apoB but is distinctly different in its composition and structure.

OBJECTIVE

Hypercholesterolemia is common in patients with anorexia nervosa (AN) despite emaciation. The objective of this study was to clarify the mechanism of hypercholesterolemia in AN.

METHODS

We measured serum lipids in 39 patients with AN and analyzed serum lipid profiles in the 24 patients in comparison with five age-matched controls.

RESULTS

Mean serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ketone bodies, apolipoprotein (apo)-A1, B, C2, C3, E, and cholesterol ester transfer protein (CETP) activity were significantly higher in patients with AN than in controls. No significant difference in serum free fatty acid (FFA) levels was observed between patients with AN and controls. CETP was accelerated in patients with AN with hypercholesterolemia. No correlation was apparent between serum levels of cholesterol and thyroid hormones.

CONCLUSIONS

Serum levels of cholesterol, CETP, and apolipoproteins decreased after weight gain, indicating that cholesterol metabolism is accelerated in patients with AN with normal serum levels of FFA.

Members of the steroid receptor superfamily are known to alter the transcription of apolipoprotein AI (apo AI), the major apoprotein of high-density lipoprotein (HDL). To assess the role of vitamin D receptor (VDR) in apo AI gene expression, we investigated the effect of 1alpha, 25-dihydroxycholecalciferol (1, 25-(OH)2 D3) as well as the vitamin D antagonist ZK-191784 (ZK), on apo AI gene expression and promoter activity in the human hepatoma cell line HepG2. Apo AI secretion and mRNA levels were both suppressed in a dose-dependent manner in HepG2 cells treated 1, 25-(OH)2 D3. This was accompanied by a similar decrease in apo AI promoter activity. Mapping of the vitamin D response element showed that suppression required a region of the apo AI gene promoter identified previously to contain site A. However, vitamin D treatment had no effect on nuclear factor binding to site A of the apo AI promoter. Treatment with vitamin D receptor antagonist ZK inhibited the ability of 1, 25-(OH)2 D3 to repress apo AI promoter activity, while higher doses of ZK increased apo AI promoter activity. ZK did not alter estradiol stimulated apo AI promoter activity. The VDR antisense ODN had no effect on apo AI promoter activity in control cells, however, it reversed the repression normally seen in cells treated with 1, 25-(OH)2D3. It is concluded that 1, 25-(OH)2 D3 suppresses apo A1 gene expression at the transcriptional level, possibly by altering coactivators or corepressors. This effect requires the VDR as well as a vitamin D response element in the apo AI promoter.

Bai Ku Yao is an isolated subgroup of the Yao minority in China. The special customs and cultures including their clothing, intraethnic marriages, corn wine and rum intakes are still completely conserved to the present day. Little is known about the association of diet and alcohol consumption with serum lipid levels in this population. The aim of this study was to compare the differences in diet, alcohol consumption, and serum lipid levels of the middle-aged and elderly between the Guangxi Bai Ku Yao and Han populations. A total of 485 subjects of Bai Ku Yao and 501 participants of Han Chinese aged 40 and over were surveyed by a stratified randomized cluster sampling. Information on dietary intake and alcohol consumption was collected by standard questionnaires. Serum lipid levels were measured. Education level, height, weight, body mass index, waist circumference, blood pressure, hypertension, and total energy, fat, protein, dietary cholesterol, and salt intakes were lower in Bai Ku Yao than in Han (P < .05-.001), whereas physical activity level, carbohydrate, vegetal protein, and total dietary fiber intakes were higher in Bai Ku Yao than in Han (P < .001 for all). Serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1, and Apo B levels were lower in Bai Ku Yao than in Han (P < .001 for all). The levels of triglyceride, HDL-C, Apo A1, and the ratio of Apo A1 to Apo B in Bai Ku Yao were higher, but the levels of LDL-C and Apo B were lower in drinkers than in nondrinkers. The levels of triglyceride, HDL-C, LDL-C, Apo A1, Apo B, and the ratio of Apo A1 to Apo B in Bai Ku Yao were also influenced by the amount of alcohol consumed (P < .05-.001). High-density lipoprotein cholesterol levels in Han were higher and LDL-C levels were lower in drinkers than in nondrinkers (P < .01 for each). Serum total cholesterol, HDL-C, and LDL-C levels in Han were also associated with the amount of alcohol consumed (P < .05-.001). The differences in the lipid levels between the two ethnic groups may partially attribute to the differences in dietary habits and alcohol consumption.

OBJECTIVE

We designed this study to investigate the effects of oral L-carnitine administration on fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and lipid parameters in patients with diabetes mellitus type II.

METHODS

The effect of L-carnitine on FPG and lipid parameters was investigated in 22 male and 13 female type II diabetic patients; the mean age +/- s.d. was 51.3 +/- 3.7 y. The patients were randomly allocated to two groups (L-carnitine and placebo group) and 1 g of L-carnitine or of placebo was given orally three times a day for a period of 12 weeks.

RESULTS

FPG in the L-carnitine group decreased significantly from 143 +/- 35 to 130 +/- 33 mg/dl (P = 0.03), and we observed a significant increase of triglycerides (TG) from 196+/-61 to 233+/-12 mg/dl (P = 0.05), of Apo A1 from 94 +/- 20 to 103 +/- 23 mg/dl (P = 0.02), and of Apo B100 from 98 +/- 18 to 108 +/- 22 mg/dl (P = 0.02) after 12 weeks of treatment. There was no significant change in LDL-C, HDL-C, HbA1C, LP(a) or total cholesterol.

CONCLUSIONS

L-Carnitine significantly lowers FPG but increases fasting triglyceride in type II diabetic patients.

The structures of two mutants (H192A and Y246F) of a mannuronate-specific alginate lyase, A1-III, from Sphingomonas species A1 complexed with a tetrasaccharide substrate [4-deoxy-L-erythro-hex-4-ene-pyranosyluronate-(mannuronate)(2)-mannuronic acid] were determined by X-ray crystallography at around 2.2 Å resolution together with the apo form of the H192A mutant. The final models of the complex forms, which comprised two monomers (of 353 amino-acid residues each), 268-287 water molecules and two tetrasaccharide substrates, had R factors of around 0.17. A large conformational change occurred in the position of the lid loop (residues 64-85) in holo H192A and Y246F compared with that in apo H192A. The lid loop migrated about 14 Å from an open form to a closed form to interact with the bound tetrasaccharide and a catalytic residue. The tetrasaccharide was bound in the active cleft at subsites -3 to +1 as a substrate form in which the glycosidic linkage to be cleaved existed between subsites -1 and +1. In particular, the O(η) atom of Tyr68 in the closed lid loop forms a hydrogen bond to the side chain of a presumed catalytic residue, O(η) of Tyr246, which acts both as an acid and a base catalyst in a syn mechanism.

Bladder cancer is clinically characterized by high recurrent rate and poor prognosis and thereby patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method for detecting and monitoring bladder cancer would thus be advantageous. In this study, by using the two-dimensional electrophoresis (2-DE) approach with subsequent mass spectrometry (MS), we demonstrated the increased expression of apolipoprotein-A1 (Apo-A1) in individual urine from patients with bladder cancer, which was confirmed by Western blot results. A further analysis of the urinary Apo-A1 levels by an enzyme-linked immunosorbent assay yielded results that were consistent with the Western blot, and suggested Apo-A1 could provide diagnostic utility to distinguish patients with bladder cancer from healthy controls at 19.21 ng/ml. Further validation assay in a larger number of urine samples (n=379) showed that Apo-A1 could be used as a biomarker to diagnosis bladder cancer with a sensitivity and specificity of 89.2% and 84.6% respectively. Moreover, the application of exfoliative urinary cytology in combination with the urine Apo-A1 detection could significantly increased the sensitivity in detecting bladder cancer. Our data showed a significant relationship of expressed Apo-A1 was established between bladder cancer and normal controls. Apo-A1 could be a potential biomarker for the diagnosis of bladder cancer.

OBJECTIVE

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that enhances degradation of the LDL receptor. While agents that inhibit PCSK9 markedly reduce atherogenic lipoproteins and show great promise for event reduction, it is unknown whether plasma PCSK9 levels predict incident cardiovascular events.

RESULTS

In a nested case-control evaluation conducted in a prospective cohort of >28 000 initially healthy American women, we measured plasma concentrations of PCSK9 at baseline among 358 participants who subsequently developed major cardiovascular events (cases) and among 358 age, smoking, and hormone replacement therapy matched participants who remained free of disease during 17 years of follow-up (controls). Proprotein convertase subtilisin/kexin type 9 level was not significantly related to smoking status, hypertension, obesity, or a family history of premature cardiovascular disease but was positively associated with apolipoprotein B-100 (r = 0.20, P< 0.001), and triglycerides (r = 0.13, P = 0.004). No associations were observed between PCSK9 and apo A1, HDLC, lipoprotein(a), or high-sensitivity C-reactive protein. Despite modest positive association with atherogenic lipids, baseline levels of PCSK9 did not predict the first cardiovascular events; the odds ratios (ORs) for future vascular events for the lowest (referent) to highest baseline quartiles of PCSK9 were 1.0, 0.94, 0.98, and 1.15 (P-trend = 0.53). In contrast, the corresponding ORs for baseline apo B levels were 1.0, 1.14, 1.34, and 1.94 (P-trend = 0.002).

CONCLUSIONS

In a large-scale primary prevention cohort, plasma levels of PCSK9 measured at baseline did not predict future cardiovascular events.

The effect of Ramadan intermittent fasting (RIF) was studied on a battery of blood lipid markers in 15 elite judo athletes during a period when they were maintaining their training load without competing. Nine-to-twelve hours postprandial serum lipid and lipoproteins were measured on five occasions: before, three times during Ramadan, and three weeks post-Ramadan. Dietary data were collected using a 24-hour recall method for three days before, during and after the Ramadan month. Mean energy intake (12.9 MJ/d) remained similar throughout the study as did the macronutrient constituents of the diet. Mean body mass was slightly reduced (2 %; p < 0.01) by the end of Ramadan due mainly to a 0.65 +/- 0.68 kg decrease in body fat (p < 0.05). The RIF produced significant changes in some of the blood lipid levels: both HDL-C and LDL-C increased by 0.12 (p < 0.01) and 0.20 mmol . l (-1) (p < 0.05), respectively. During Ramadan, mean non-esterified fatty acid (NEFA) levels decreased from 0.73 to 0.28 mmol . l (-1) (p < 0.01) during the first week, then increased (p < 0.05) to 1.22 mmol . l (-1) over the middle of Ramadan and recovered to pre-Ramadan concentrations for the end and the post-Ramadan periods. Apolipoprotein A1 (Apo-A1) levels were significantly elevated at the end (p < 0.01) and the post-Ramadan periods (p < 0.05). Three weeks after Ramadan, blood levels of glucose, NEFA, Apo-A1, and Apo-B did not return to the values observed before Ramadan. In conclusion, the present results show that the combination of the change in diet pattern during Ramadan, along with intense exercise training, induced a significant decrease in body mass associated with a reduction in body fat and changes in some of the serum lipids and lipoproteins. Nevertheless, all the measured serum parameters remained within normal levels for young and active individuals. The volunteers, in this study, were able to maintain a constant training load during RIF.

OBJECTIVE

What are the relationships between apolipoprotein (apo) A-I and apoB concentrations, the apoB/apoA-I ratio and the prevalences of dyslipidemia and metabolic syndrome (MS) in south-west Chinese women with polycystic ovary syndrome (PCOS).

CONCLUSIONS

There is a relatively high incidence of dyslipidemia and MS in south-west Chinese women with PCOS, especially in patients without hyperandrogenism. Patients with dyslipidemia are more obese, and have a more adverse glucose and lipid metabolic profile and higher apoB levels and apoB/apoA-I ratio. The increased apoB levels and apoB/A1 ratio and the MS are strongly associated with PCOS, suggesting that there is an increased risk of cardiovascular diseases in these patients.

BACKGROUND

Dyslipidemia and MS have been widely studied in women with PCOS, but to date no data from south-west Chinese subjects have been available. The apoB/apoA-I ratio has been reported to be strongly associated with MS and insulin resistance (IR) and to be a reliable parameter that reflects lipid disturbances and the potential to develop atherosclerosis, but its relationship with PCOS is unclear. DESIGN This case-control study included 406 patients with PCOS and 342 control women between 17 and 40 years of age from a population in south-west China during 2006-2011.

METHODS

The diagnosis of PCOS was based on the revised 2003 Rotterdam criteria. The control group, consisting of women with infertility due to a Fallopian obstruction or the husband's infertility, women undergoing a pre-pregnancy check and healthy volunteers, was recruited from the same hospital during the same period. All women were not taking any medication known to affect carbohydrate or lipid or hormone metabolism for at least 3 months prior to the study, and were studied during the follicular phase of their menstrual cycle. MS was assessed by the National Cholesterol Education Program-Adult treatment Panel (NCEP-ATP) III criteria modified for Asian populations. Dyslipidemia was defined by one or more of the following conditions: fasting total cholesterol≥5.7 mmol/l, fasting triglycerides (TG)≥1.7 mmol/l, fasting high-density lipoprotein cholesterol (HDL-C)<1.29 mmol/l or fasting low-density lipoprotein cholesterol (LDL-C)≥3.6 mmol/l.

RESULTS

The prevalence of dyslipidemia in patients with PCOS was 52.96%, about two times than that in the controls, 28.95%. The most common components of dyslipidemia in patients with PCOS were decreased HDL-C (41.13%) and increased TG (24.14%). PCOS patients with dyslipidemia had significantly higher TG/HDL-C ratios, and lower HDL-C and apoA-I levels when compared with the controls or patients without dyslipidemia, and had significantly higher BMIs, fasting insulin concentrations, 2-h insulin and glucose levels, homeostatic model assessment IR, TG levels, LDL-C levels, atherogenic indexes, apoB concentrations and apoB/apoA-I ratios when compared with all of the control women, with or without dyslipidemia and patients without dyslipidemia. The frequency of MS in patients with PCOS was 25.62%, more than five times than that in the controls. The main two risk factors were increased waist circumference and low HDL-C levels. In the four PCOS phenotypes based on the Rotterdam criteria, the oligo- and/or anovulation+PCO presented the highest prevalence of dyslipidemia (66.14%) and MS (34.65%). Binary logistic regression analysis showed that increased apoB levels, an increased apoB/apoA-I ratio and MS was strongly associated with PCOS (odds ratio=17.41, 27.16 and 7.66, 95% confidence interval: 6.93-43.74, 9.46-77.93 and 4.32-13.57, respectively) after adjustment for age.

CONCLUSIONS

The relatively minor limitations of this study are discussed within the paper. GENERALISABILITY TO OTHER POPULATIONS: The metabolic patterns found in south-west Chinese with PCOS are compared with that of other populations.

BACKGROUND

This work was supported by Chinese National Natural Science Foundation (81070463), Program for Changjiang Scholars and Innovative Research Team in University (IRT0935), and Research Seed Fund from West China Second Hospital of Sichuan University (to H.B.). There are no any competing interests.

BACKGROUND

N/A.

This study investigated the effectiveness of Qigong on blood pressure and several blood lipids, such as high-density lipoprotein (HDL) cholesterol, Apolipoprotein A1 (APO-A1), total cholesterol (TC), and triglycerides (TG) in hypertensive patients. Thirty-six patients were randomly divided into either the Qigong group, or a wait-listed control group. Blood pressures decreased significantly after eight weeks of Qigong. The levels of TC, HDL, and APO-A1 were changed significantly in the Qigong group post-treatment compared with before treatment. In summary. Qigong acts as an antihypertensive and may reduce blood pressure by the modulation of lipid metabolism.

BACKGROUND

More than a million diagnostic cardiac catheterizations are performed annually in the US for evaluation of coronary artery anatomy and the presence of atherosclerosis. Nearly half of these patients have no significant coronary lesions or do not require mechanical or surgical revascularization. Consequently, the ability to rule out clinically significant coronary artery disease (CAD) using low cost, low risk tests of serum biomarkers in even a small percentage of patients with normal coronary arteries could be highly beneficial.

METHODS

Serum from 359 symptomatic subjects referred for catheterization was interrogated for proteins involved in atherogenesis, atherosclerosis, and plaque vulnerability. Coronary angiography classified 150 patients without flow-limiting CAD who did not require percutaneous intervention (PCI) while 209 required coronary revascularization (stents, angioplasty, or coronary artery bypass graft surgery). Continuous variables were compared across the two patient groups for each analyte including calculation of false discovery rate (FDR ≤ 1%) and Q value (P value for statistical significance adjusted to ≤ 0.01).

RESULTS

Significant differences were detected in circulating proteins from patients requiring revascularization including increased apolipoprotein B100 (APO-B100), C-reactive protein (CRP), fibrinogen, vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), resistin, osteopontin, interleukin (IL)-1β, IL-6, IL-10 and N-terminal fragment protein precursor brain natriuretic peptide (NT-pBNP) and decreased apolipoprotein A1 (APO-A1). Biomarker classification signatures comprising up to 5 analytes were identified using a tunable scoring function trained against 239 samples and validated with 120 additional samples. A total of 14 overlapping signatures classified patients without significant coronary disease (38% to 59% specificity) while maintaining 95% sensitivity for patients requiring revascularization. Osteopontin (14 times) and resistin (10 times) were most frequently represented among these diagnostic signatures. The most efficacious protein signature in validation studies comprised osteopontin (OPN), resistin, matrix metalloproteinase 7 (MMP7) and interferon γ (IFNγ) as a four-marker panel while the addition of either CRP or adiponectin (ACRP-30) yielded comparable results in five protein signatures.

CONCLUSIONS

Proteins in the serum of CAD patients predominantly reflected (1) a positive acute phase, inflammatory response and (2) alterations in lipid metabolism, transport, peroxidation and accumulation. There were surprisingly few indicators of growth factor activation or extracellular matrix remodeling in the serum of CAD patients except for elevated OPN. These data suggest that many symptomatic patients without significant CAD could be identified by a targeted multiplex serum protein test without cardiac catheterization thereby eliminating exposure to ionizing radiation and decreasing the economic burden of angiographic testing for these patients.

The apolipoprotein A1 gene polymorphism (G-75A and C+83T) was studied in 100 subjects (50 patients diagnosed with myocardial infarction and 50 healthy subjects). Serum apolipoprotein (apo) A1 and apo B levels were estimated immunoturbidometrically. Extracted DNA from blood was amplified by polymerase chain reaction, digested with MspI restriction enzyme, run on 8% polyacrylamide gel, and restriction fragment length polymorphism was studied by using a gel documentation system. Serum (mean +/- SD) apo A1 levels were significantly higher in control subjects than the study group (100.80 +/- 7.06 mg/dL [1.0 +/- 0.07 g/L] and 72.56 +/- 9.86 mg/dL [0.73 +/- 0.1 g/L], respectively; P < .0001), whereas apo B levels were significantly lower (72.12 +/- 11.32 mg/dL [0.7 +/- 0.1 g/L] and 97.45 +/- 9.04 mg/dL [1.0 +/- 0.09 g/L], respectively; P < .0001). The G allele frequency at the -75-base-pair (bp) site was higher in the study group (79%) compared with the control group (58%). The T allele frequency at the +83-bp site was higher in the study group (56%) than in the control group (32%). G at -75 bp upstream from the start of transcription and T at +83 bp in the first intron may be susceptibility alleles for myocardial infarction.

OBJECTIVE

Statins and fibrates alter lipids, apolipoproteins and inflammatory markers in persons without HIV. The objective of this study was to evaluate changes in lipoproteins, apolipoproteins and other markers of inflammation with the use of pravastatin and fenofibrate.

METHODS

Evaluation of participants in ACTG A5087, a randomized trial of pravastatin 40 mg/day or fenofibrate 200 mg/day for the treatment of dyslipidemia. Participants that failed single-agent therapy at week 12 were given the combination.

METHODS

Participants with available specimens were tested for apolipoproteins A1 and B, adiponectin, plasminogen-activator inhibitor type 1 (PAI-1), P-selectin, and high-sensitivity C-reactive protein (hs-CRP).

RESULTS

74 participants (37 per randomized arm) received either pravastatin or fenofibrate for 12 weeks with 60 receiving combination treatment from weeks 12-48. There were no significant changes in hs-CRP, PAI-1, and P-selectin. From baseline to week 12, the median Apo B levels (-8 mg/dL, P=0.01 for fenofibrate and -27 mg/dL, P<0.01 for pravastatin) and ApoB/A1 ratios (-0.16, P<0.01 for both arms) significantly decreased. From baseline to week 48, median adiponectin (-1 ng/dL, P<0.01), Apo B (-22 mg/dL, P<0.01) and Apo B/A1 ratios (-0.2, P<0.01) all decreased in those who went on combination therapy, whereas Apo A1 (9.5 mg/dL, P=0.01) levels increased.

CONCLUSIONS

Treatment with pravastatin or fenofibrate improves the atherogenic lipid profile within the first 12 weeks and is sustained through 48 weeks with combination therapy. Adiponectin levels decrease with lipid-lowering therapy. However, markers of inflammation and platelet activation were not appreciably changed suggesting that the biologic properties of these agents differ in persons with HIV infection.

The effects of a red wine phenolic extract (PE) on plasma lipoproteins and early atherosclerosis were studied in hamsters. Hamsters (n = 32) were divided into 4 groups of 8 and fed an atherogenic diet for 8 wk. They received by force- feeding 7.14 mL/(kg. d) PE in 2.6 mol/L ethanol (E + PE) or PE in water (W + PE), mimicking a moderate consumption of red wine or alcohol-free red wine [30.4 mg/(kg. d)], or 2.6 mol/L ethanol (E-PE) or water (W-PE) as their respective controls. Plasma cholesterol and triglyceride concentrations were lower in groups that consumed PE. The decrease in plasma apolipoprotein (Apo) B concentration was due mainly to PE and was significantly lower in Group E + PE than in Group E-PE (-7.5%) and in Group W + PE than in Group W-PE (-40%). Apo-A1 was not affected. PE significantly increased plasma antioxidant capacity by 9% in Group E + PE and 18% in Group W + PE compared with their respective controls. Liver glutathione peroxidase activity was 67% greater in the group receiving PE in water compared with the group given water; there was no effect when PE was given in ethanol relative to its control. Aortic fatty streak area (AFSA) was significantly reduced in the groups receiving PE in ethanol (-32%) or PE in water (-29%) in comparison with their respective controls. Ethanol significantly reduced AFSA by 60% (Group E-PE vs. Group W-PE) or 62% (Group E + PE vs. Group W + PE). These data suggest that ethanol is a complementary component of phenolics in the benefits of red wine for hamsters and that chronic ingestion of PE in ethanol prevents the development of atherosclerosis through several mechanisms. With moderate consumption of red wine, ethanol can improve the effects of phenolic compounds. However, alcohol-free red wine appears to be a very good alternative to red wine.

Robust methods were employed, using data from a single large pedigree, to screen serum apolipoprotein A1 and B levels, serum lipoprotein cholesterol levels, and ratios of serum lipoprotein cholesterol fractions to apolipoprotein A1 and B levels for genetic linkage to 31 polymorphic markers. Segregation analyses were performed for each of the apolipoprotein and lipoprotein cholesterol fractions to obtain estimates for use in applying likelihood methods of linkage analysis. Trait-marker combinations for which linkages were suggested from the robust methods were then reexamined for linkage using the likelihood (lod score) method. Results from the segregation analyses were consistent with major gene determination of apo B and HDL-C levels, the HDL-C to apo A1 ratio, the LDL-C to apo B ratio, and a measure of relative content of cholesterol in HDL-C and LDL-C. Linkage between haptoglobin and the HDL-C/apo A1 ratio was suggested, with a lod score of 1.72 at theta = 0.05.