Several previous epidemiologic studies have shown that high blood levels of carotenoids may be protective against early atherosclerosis, but results have been inconsistent. We assessed the association between atherosclerotic progression, measured by intima-media thickness of the common carotid artery wall, and serum levels of carotenoids.We studied the effect of carotenoids on progression of early atherosclerosis in a population-based study. The association between concentrations of serum carotenoids, and intima-media thickness of the common carotid artery wall was explored in 840 middle-aged men (aged 46-65 years) from Eastern Finland. Ultrasonography of the common carotid arteries were performed at baseline and 7-year follow-up. Serum levels of carotenoids were analyzed at baseline. Changes in mean and maximum intima media thickness of carotid artery wall were related to baseline serum carotenoid levels in covariance analyses adjusted for covariates.In a covariance analysis with adjustment for age, ultrasound sonographer, maximum intima media thickness, examination year, body mass index, systolic blood pressure, smoking, physical activity, serum LDL cholesterol, family history of coronary heart disease, antihypertensive medication and serum high sensitivity C-reactive protein, 7-year change in maximum intima media thickness was inversely associated with lycopene (p = 0.005), α-carotene (p = 0.002) and β-carotene (p = 0.019), respectively.The present study shows that high serum concentrations of carotenoids may be protective against early atherosclerosis.

Cholesterol oxidase production (COD) by a new isolate characterized as Streptomyces sp. was studied in different production media and fermentation conditions. Individual supplementation of 1 % maltose, lactose, sucrose, peptone, soybean meal and yeast extract enhanced COD production by 80-110 % in comparison to the basal production medium (2.4 U/ml). Supplementation of 0.05 % cholesterol (inducer) enhanced COD production by 150 %. COD was purified 14.3-fold and its molecular weight was found to be 62 kDa. Vmax (21.93 μM/min mg) and substrate affinity Km (101.3 μM) suggested high affinity of the COD for cholesterol. In presence of Ba(2+) and Hg(2+) the enzyme activity was inhibited while Cu(2+) enhanced the activity nearly threefold. Relative activity of the enzyme was found maximum in triton X-100 whereas sodium dodecyl sulfate inactivated the enzyme. The enzyme activity was also inhibited by the thiol-reducing reagents like Dithiothreitol and β-mercaptoethanol. The COD showed moderate stability towards all organic solvents except acetone, benzene and chloroform. The activity increased in presence of isopropanol and ethanol. The enzyme was most active at pH 7 and 37 °C temperature. This organism is not reported to produce COD.

Icariin is a major active component isolated from the traditional Chinese herb Epimedium brevicornum, with a wide range of pharmacological and biological activities. In this paper, we investigated the effects of icariin on hyperlipidemia, and further evaluated whether icariin could improve unfavorable hemorheological parameters, attenuate platelet activation and facilitate the balance between plasmic plasminogen activator inhibitor-1 and tissue-type plasminogen activator activities in rabbits fed a high-cholesterol diet. Icariin reduced the levels of serum total cholesterol and low-density lipoprotein cholesterol, as well as the atherosclerotic burden. In addition, this compound has been found to improve the imbalance between plasmic plasminogen activator inhibitor-1 and tissue-type plasminogen activator activities, reduce platelet adhesiveness and aggregation and modulate unfavorable hemorheological variables in hypercholesterolemia. In conclusion, icariin has lipid-lowering effects and may be used in the treatment and prevention of thrombosis in the atherosclerotic process.

Atherosclerotic diseases, such as coronary artery disease and peripheral artery disease, are systemic disorders and among the leading causes of mortality and morbidity throughout the world. However, the exact pathophysiological mechanisms underlying the development of atherosclerosis remain unknown; currently, atherosclerosis is thought to involve an inflammatory process. Systemic inflammatory reactions and accumulation of immune cells in atherosclerotic lesions in situ are considered essential. We have comprehensively analyzed autoantibodies in patients with atherosclerosis by means of a newly developed high-throughput autoantibody analysis system. A wide range of autoantibodies was found in sera from patients with atherosclerosis. After we statistically analyzed the titers of each autoantibody with conventional techniques, the results underwent text-mining analyses based on natural language processing. Combinatory analysis revealed a close association between anti-interleukin (IL)-5 antibody and atherosclerosis. Titers of anti-IL-5 antibodies and serum IL-5 concentrations were also closely associated with other risk factors, such as low-density lipoprotein cholesterol, serum creatinine, fasting plasma glucose, gender, and age, suggesting that suppressed IL-5 function mediated by autoantibodies in patients with atherosclerosis plays an important role in the disease process. To validate the clinical significance of these findings, we computed the specificity and sensitivity of titers of anti-IL-5 autoantibodies for human atherosclerosis. When antibody titers of 1.49 were assumed to predict the presence of atherosclerosis, the sensitivity was 95.0% and the specificity 91.0%, with an area under the curve of 0.940. Our results provide important clues to understanding the role of autoantibody-mediated immune reactions in human atherosclerosis and suggest novel therapeutic opportunities for management of the disease.-Ishigami, T., Abe, K., Aoki, I., Minegishi, S., Ryo, A., Matsunaga, S., Matsuoka, K., Takeda, H., Sawasaki, T., Umemura, S., and Endo, Y. Anti-interleukin-5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin-5 levels.

ABSTRACT

BACKGROUND:

There is growing evidence from animal models that intermittent hypoxemia (IH) may induce dyslipidemia. Altered lipid metabolism may contribute to the increased cardiovascular risk observed in obstructive sleep apnea (OSA). In this multisite cross-sectional study, we tested the hypothesis of an independent association between nocturnal IH and dyslipidemia in OSA.

METHODS:

Fasting serum lipid levels were measured in 2,081 patients (638 females) undergoing nocturnal recording for clinical suspicion of OSA. Multivariate regression analyses were performed to evaluate the independent associations between oxygen desaturation index (ODI) and lipid profile after adjustment for potential confounders including components of the metabolic syndrome (MS) or MS itself. Adjusted odds ratio (OR) for metabolic dyslipidemia (MD) (triglycerides [TG]≥150 mg/dL and high-density lipoprotein cholesterol [HDL-c]≤50 mg/dL for women and ≤40 mg/dL for men) according to quartiles of ODI were determined by logistic regression.

RESULTS:

Total cholesterol and LDL cholesterol were not associated with ODI. In contrast, nocturnal IH and OSA severity were associated with higher TG levels and lower HDL-c levels after adjustment for confounding factors. The association between ODI and TG and HDL-c was independent of the MS. Adjusted OR (95% confidence intervals) for MD were 1 (reference), 1.56 (1.24 to 1.96), 1.72 (1.29 to 2.29), and 1.93 (1.55 to 2.41) for ODI≤7, >7 to ≤18, >18 to ≤38, and >38, respectively (P<0.0001 for linear trend).

CONCLUSIONS:

Nocturnal IH is independently associated with MD that may predispose OSA patients to a higher risk of cardiovascular disease.

Lipid rafts in eukaryotic cells are sphingolipid and cholesterol-rich, ordered membrane regions that have been postulated to play roles in many membrane functions, including infection. We previously demonstrated the existence of cholesterol-lipid-rich domains in membranes of the prokaryote, B. burgdorferi, the causative agent of Lyme disease [LaRocca et al. (2010) Cell Host & Microbe 8, 331-342]. Here, we show that these prokaryote membrane domains have the hallmarks of eukaryotic lipid rafts, despite lacking sphingolipids. Substitution experiments replacing cholesterol lipids with a set of sterols, ranging from strongly raft-promoting to raft-inhibiting when mixed with eukaryotic sphingolipids, showed that sterols that can support ordered domain formation are both necessary and sufficient for formation of B. burgdorferi membrane domains that can be detected by transmission electron microscopy or in living organisms by Förster resonance energy transfer (FRET). Raft-supporting sterols were also necessary and sufficient for formation of high amounts of detergent resistant membranes from B. burgdorferi. Furthermore, having saturated acyl chains was required for a biotinylated lipid to associate with the cholesterol-lipid-rich domains in B. burgdorferi, another characteristic identical to that of eukaryotic lipid rafts. Sterols supporting ordered domain formation were also necessary and sufficient to maintain B. burgdorferi membrane integrity, and thus critical to the life of the organism. These findings provide compelling evidence for the existence of lipid rafts and show that the same principles of lipid raft formation apply to prokaryotes and eukaryotes despite marked differences in their lipid compositions.

Aims:

The current study aim was to elucidate the anti-hypoglycemic role and mechanism of inducible nitric oxide synthase (iNOS) under inflammatory stress.

Methods:

Liver inflammatory stress was induced in wild-type (WT) and iNOS-knockout (iNOS-/-) mice by LPS (5 mg/Kg) with and without the background of non alcoholic steatohepatitis (NASH)-Induced by high cholesterol diet (HCD, 6 weeks).

Results:

HCD led to steatohepatitis in WT and iNOS-/- mice. LPS administration caused marked liver inflammatory damage only in cholesterol-fed mice, which was further exacerbated in the absence of iNOS. Glucose homeostasis was significantly impaired and included fatal hypoglycemia and inhibition of glycogen decomposition. In iNOS-/- hypoxia-inducible factor-1 (HIF1) signaling was impaired compared to control WT. Using hydrodynamic gene transfer method HIF1α was expressed in the livers of iNOS-/- mice, and significantly ameliorated cholesterol and LPS-induced liver damage. WT mice overexpressing HIF1α exhibited higher blood glucose levels and lower glycogen contents after LPS injection. Conversely, induction of HIF1α was not effective in preventing LPS-induced glucose lowering effect in iNOS-/- mice. The critical role of NO signaling in hepatocytes glucose output mediated by HIF1 pathway was also confirmed in-vitro. Results also demonstrated increased oxidative stress and reduced heme oxygenase-1 mRNA in the livers of iNOS-/- mice. Furthermore, the amounts of plasma tumor necrosis factor-α (TNFα) and intrahepatic TNFα mRNA were significantly elevated in the absence of iNOS. Innovation and

Conclusion:

these data highlight the essential role of iNOS in the glycemic response to LPS in NASH conditions and argues for the beneficial effects of iNOS.

The prevalence of metabolic syndrome (MetS) is increasing among children and adolescents. However, the prevalence of this disorder varies based on its different definitions. This study aimed to determine the prevalence of MetS in Iranian adolescents in junior high and high schools according to the definitions provided by the International Diabetes Federation (IDF) and De Ferranti.Overall, 1039 junior high school and 953 high school students were selected using multistage random sampling. Demographic data was collected using validated questionnaires. Fasting blood sugar, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were determined. Waist circumference and blood pressure were measured by trained individuals. Subjects with MetS were selected according to two definitions provided by the IDF and De Ferranti. Chi-square and Fisher's exact tests were used to compare the prevalence of MetS and its components based on sex, school level, and the two definitions.The mean age of junior high and high school students was 13.11 ± 1.21ad 15.93 ± 1.07 years old, respectively. The prevalence of MetS among all participants was 4.8% and 12.7% according to the definitions by the IDF and De Ferranti, respectively. It was significantly higher among boys compared to girls. According to the IDF definition, low HDL-C and hypertension were the most frequent components. Based on the De Ferranti, abdominal obesity and hypertriglyceridemia were the most frequent components.The prevalence of MetS was higher in both groups of students based on De Ferranti definition compared to the IDF definition. The prevalence was not significantly different in boys and girls. Further studies to investigate the most suitable definition of MetS for Iranian adolescents are necessary.

Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans.