Trimethylamine N-oxide levels are associated with NASH in obese subjects with type 2 diabetes.

AIMS: Trimethylamine N-oxide (TMAO), choline and betaine serum levels have been associated with metabolic diseases including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). These associations could be mediated by insulin resistance. However, the relationships among these metabolites, insulin resistance and NAFLD have not been thoroughly investigated. Moreover, it has recently been suggested that TMAO could play a role in NAFLD by altering bile acid metabolism. We examined the association between circulating TMAO, choline and betaine levels and NAFLD in obese subjects. METHODS: Serum TMAO, choline, betaine and bile acid levels were measured in 357 Mexican obese patients with different grades of NAFLD as determined by liver histology. Associations of NAFLD with TMAO, choline and betaine levels were tested. Moreover, association of TMAO levels with non-alcoholic steatohepatitis (NASH) was tested separately in patients with and without T2D. RESULTS: TMAO and choline levels were significantly associated with NAFLD histologic features and NASH risk. While increased serum TMAO levels were significantly associated with NASH in patients with T2D, in non-T2D subjects this association lost significance after adjusting for sex, BMI and HOMA2-IR. Moreover, circulating secondary bile acids were associated both with increased TMAO levels and NASH. CONCLUSIONS: In obese patients, circulating TMAO levels were associated with NASH mainly in the presence of T2D. Functional studies are required to evaluate the role of insulin resistance and T2D in this association, both highly prevalent in NASH patients.

Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis.

BACKGROUND AND AIMS: Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model. METHODS AND RESULTS: The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances. CONCLUSION: The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall.

Flavin monooxygenase 3, the host hepatic enzyme in the metaorganismal trimethylamine N-oxide-generating pathway, modulates platelet responsiveness and thrombosis risk.

Essentials Microbe-dependent production of trimethylamine N-oxide (TMAO) contributes to thrombosis risk. The impact of host flavin monooxygenase 3 (FMO3) modulation on platelet function is unknown. Genetic manipulation of FMO3 in mice alters systemic TMAO levels and thrombosis potential. Genetic manipulation of FMO3 is associated with alteration of gut microbial community structure. SUMMARY: Background Gut microbes play a critical role in the production of trimethylamine N-oxide (TMAO), an atherogenic metabolite that impacts platelet responsiveness and thrombosis potential. Involving both microbe and host enzymatic machinery, TMAO generation utilizes a metaorganismal pathway, beginning with ingestion of trimethylamine (TMA)-containing dietary nutrients such as choline, phosphatidylcholine and carnitine, which are abundant in a Western diet. Gut microbial TMA lyases use these nutrients as substrates to produce TMA, which upon delivery to the liver via the portal circulation, is converted into TMAO by host hepatic flavin monooxygenases (FMOs). Gut microbial production of TMA is rate limiting in the metaorganismal TMAO pathway because hepatic FMO activity is typically in excess. Objectives FMO3 is the major FMO responsible for host generation of TMAO; however, a role for FMO3 in altering platelet responsiveness and thrombosis potential in vivo has not yet been explored. Methods The impact of FMO3 suppression (antisense oligonucleotide-targeting) and overexpression (as transgene) on plasma TMAO levels, platelet responsiveness and thrombosis potential was examined using a murine FeCl3 -induced carotid artery injury model. Cecal microbial composition was examined using 16S analyses. Results Modulation of FMO3 directly impacts systemic TMAO levels, platelet responsiveness and rate of thrombus formation in vivo. Microbial composition analyses reveal taxa whose proportions are associated with both plasma TMAO levels and in vivo thrombosis potential. Conclusions The present studies demonstrate that host hepatic FMO3, the terminal step in the metaorganismal TMAO pathway, participates in diet-dependent and gut microbiota-dependent changes in both platelet responsiveness and thrombosis potential in vivo.

Novel MYC-driven medulloblastoma models from multiple embryonic cerebellar cells.

Group3 medulloblastoma (MBG3) that predominantly occur in young children are usually associated with MYC amplification and/or overexpression, frequent metastasis and a dismal prognosis. Physiologically relevant MBG3 models are currently lacking, making inferences related to their cellular origin thus far limited. Using in utero electroporation, we here report that MBG3 mouse models can be developed in situ from different multipotent embryonic cerebellar progenitor cells via conditional expression of Myc and loss of Trp53 function in several Cre driver mouse lines. The Blbp-Cre driver that targets embryonic neural progenitors induced tumors exhibiting a large-cell/anaplastic histopathology adjacent to the fourth ventricle, recapitulating human MBG3. Enforced co-expression of luciferase together with Myc and a dominant-negative form of Trp53 revealed that GABAergic neuronal progenitors as well as cerebellar granule cells give rise to MBG3 with their distinct growth kinetics. Cross-species gene expression analysis revealed that these novel MBG3 models shared molecular characteristics with human MBG3, irrespective of their cellular origin. We here developed MBG3 mouse models in their physiological environment and we show that oncogenic insults drive this MB subgroup in different cerebellar lineages rather than in a specific cell of origin.

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

BACKGROUND AND OBJECTIVES: Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis. MATERIALS AND METHODS: Male C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay. RESULTS: Lentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects. CONCLUSIONS: Cathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.

Inhibition of a novel fibrogenic factor Tl1a reverses established colonic fibrosis.

Intestinal fibrostenosis is among the hallmarks of severe Crohn's disease. Patients with certain TNFSF15 (gene name for TL1A) variants over-express TL1A and have a higher risk of developing strictures in the small intestine. In addition, sustained Tl1a expression in mice leads to small and large intestinal fibrostenosis under colitogenic conditions. The aim of this study was to determine whether established murine colonic fibrosis could be reversed with Tl1a antibody (Ab). Treatment with neutralizing Tl1a Ab reversed colonic fibrosis back to the original pre-inflamed levels, potentially as a result of lowered expression of connective tissue growth factor, Il31Ra, transforming growth factor ß1 and insulin-like growth factor-1. In addition, blocking Tl1a function by either neutralizing Tl1a Ab or deletion of death domain receptor 3 (Dr3) reduced the number of fibroblasts and myofibroblasts, the primary cell types that mediate tissue fibrosis. Primary intestinal myofibroblasts expressed Dr3 and functionally responded to direct Tl1a signaling by increasing collagen and Il31Ra expression. These data demonstrated a direct role for TL1A-DR3 signaling in tissue fibrosis and that modulation of TL1A-DR3 signaling could inhibit gut fibrosis.

MRI surrogates for molecular subgroups of medulloblastoma.

BACKGROUND AND PURPOSE: Recently identified molecular subgroups of medulloblastoma have shown potential for improved risk stratification. We hypothesized that distinct MR imaging features can predict these subgroups. MATERIALS AND METHODS: All patients with a diagnosis of medulloblastoma at one institution, with both pretherapy MR imaging and surgical tissue, served as the discovery cohort (n = 47). MR imaging features were assessed by 3 blinded neuroradiologists. NanoString-based assay of tumor tissues was conducted to classify the tumors into the 4 established molecular subgroups (wingless, sonic hedgehog, group 3, and group 4). A second pediatric medulloblastoma cohort (n = 52) from an independent institution was used for validation of the MR imaging features predictive of the molecular subtypes. RESULTS: Logistic regression analysis within the discovery cohort revealed tumor location (P < .001) and enhancement pattern (P = .001) to be significant predictors of medulloblastoma subgroups. Stereospecific computational analyses confirmed that group 3 and 4 tumors predominated within the midline fourth ventricle (100%, P = .007), wingless tumors were localized to the cerebellar peduncle/cerebellopontine angle cistern with a positive predictive value of 100% (95% CI, 30%-100%), and sonic hedgehog tumors arose in the cerebellar hemispheres with a positive predictive value of 100% (95% CI, 59%-100%). Midline group 4 tumors presented with minimal/no enhancement with a positive predictive value of 91% (95% CI, 59%-98%). When we used the MR imaging feature-based regression model, 66% of medulloblastomas were correctly predicted in the discovery cohort, and 65%, in the validation cohort. CONCLUSIONS: Tumor location and enhancement pattern were predictive of molecular subgroups of pediatric medulloblastoma and may potentially serve as a surrogate for genomic testing.

Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Split-dose administration of thiopurine drugs: a novel and effective strategy for managing preferential 6-MMP metabolism.

BACKGROUND: Mercaptopurine and azathioprine (AZA) are efficacious in treating IBD. 6-tioguanine (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Some IBD patients exhibit dose-limiting preferential 6-MMP production, which may lead to undesired side effects and impact efficacy. AIM: To review the outcomes of thiopurine split-dosing in patients with preferential 6-MMP metabolism. METHODS: A retrospective chart review of 179 IBD patients treated at the Cedars-Sinai IBD Center with AZA or mercaptopurine was performed. Preferential 6-MMP metabolisers with 6-MMP levels greater than 7000 pmol/8 × 10(8) erythrocytes who underwent split-dosing were identified and assessed for biochemical and clinical responses to these dose modifications. RESULTS: A total of 20 of 179 patients met the criteria for preferential 6-MMP metabolism and underwent thiopurine split-dosing. Dividing the total daily thiopurine dose led to a reduction in 6-MMP levels (11785 vs. 5324 pmol/8 × 10(8) erythrocytes; P < 0.0001) without negatively affecting clinical disease activity or 6-TGN levels (239 vs. 216 pmol/8 × 10(8) erythrocytes; P = N.S.) and led to resolution of 6-MMP associated side effects (elevated transaminases, leucopenia and flu-like symptoms) in all but two patients. After mean follow-up of 36 months, 12 patients remained in clinical remission on split-dose mercaptopurine. Five of the remaining eight patients escalated to anti-TNF therapy, two progressed to surgery, and one switched to tioguanine therapy. CONCLUSION: Split-dose administration of mercaptopurine/AZA represents an alternative option in IBD patients with preferential 6-MMP metabolism who might otherwise require steroid exposure or escalation of therapy.

PON3 is upregulated in cancer tissues and protects against mitochondrial superoxide-mediated cell death.

To achieve malignancy, cancer cells convert numerous signaling pathways, with evasion from cell death being a characteristic hallmark. The cell death machinery represents an anti-cancer target demanding constant identification of tumor-specific signaling molecules. Control of mitochondrial radical formation, particularly superoxide interconnects cell death signals with appropriate mechanistic execution. Superoxide is potentially damaging, but also triggers mitochondrial cytochrome c release. While paraoxonase (PON) enzymes are known to protect against cardiovascular diseases, recent data revealed that PON2 attenuated mitochondrial radical formation and execution of cell death. Another family member, PON3, is poorly investigated. Using various cell culture systems and knockout mice, here we addressed its potential role in cancer. PON3 is found overexpressed in various human tumors and diminishes mitochondrial superoxide formation. It directly interacts with coenzyme Q10 and presumably acts by sequestering ubisemiquinone, leading to enhanced cell death resistance. Localized to the endoplasmic reticulum (ER) and mitochondria, PON3 abrogates apoptosis in response to DNA damage or intrinsic but not extrinsic stimulation. Moreover, PON3 impaired ER stress-induced apoptotic MAPK signaling and CHOP induction. Therefore, our study reveals the mechanism underlying PON3's anti-oxidative effect and demonstrates a previously unanticipated function in tumor cell development. We suggest PONs represent a novel class of enzymes crucially controlling mitochondrial radical generation and cell death.

CD161 DEFINES EFFECTOR T CELLS THAT EXPRESS LIGHT AND RESPOND TO TL1A-DR3 SIGNALING.

Expression of NK cell markers identifies pro-inflammatory T cell subsets in the liver and intestinal immune compartments. Specifically, CD161 is expressed on Th17 cells which play an important role in the regulation of mucosal inflammation. In this study, we characterized human peripheral blood CD161+ T cells as an effector population partially resembling a gut T cell phenotype. CD161+ CD4+ T cells express the gut-associated TNF family member, LIGHT, and respond to crosslinking of DR3, a receptor to another gut-associated cytokine, TL1A. Robust IFN-γ production in response to DR3 signaling correlated with enhanced expression of surface DR3 on CD161+ T cells and co-stimulation with IL12 and IL18. CD161+ T cell effector function was directly demonstrated by activation of responder monocytes in co-culture leading to CD40 upregulation and CD14 downregulation. CD161+ T cells reciprocally responded to activated monocytes, inducing expression of activation marker, CD69, and production of IL2 and IFN-γ, further demonstrating effective CD161+ T cell cross-talk with monocytes. Finally, CD161 defined a subset of T cells that co-express CD56, a second NK marker. Our findings implicate human CD161+ T cells in gut-associated signaling mechanisms, and suggest a monocyte mediated effector function in mucosal inflammation.

Survey and risk assessment of trace elements in foods from Taiwan containing red mould rice (Monascus) by ICP-MS.

The concentrations of seven trace elements (As, Cd, Cr, Pb, Se, Cu and Zn) in 93 red mould rice (Monascus) food samples in Taipei, Taiwan, were determined by inductively coupled plasma-mass spectrometry (ICP-MS) after wet digestion. The results, calculated in mg kg(-1) (wet weight) for each sample, revealed the general scenario of food safety in Taiwan: As (0.005-12.04), Cd (<0.0005-2.22), Cr (0.014-6.95), Cu (0.012-8.70), Pb (0.001-0.64), Se (<0.001-1.29) and Zn (0.020-67.02). Three food samples were identified with As concentrations higher than regulatory limits: a dietary supplement sample and a seaweed sample with As concentrations that exceeded the limit of Taiwan's health food standard of 2 mg kg(-1), and a canned eel sample with an As concentration that exceeded the limit of Canada's fish standard of 3.5 mg kg(-1). This study suggests that the estimated intakes of these seven trace elements from the consumption of foods containing Monascus pose little risk, as the trace element contents in the majority of samples were lower than the permissible/tolerable intakes per week according to the guidelines recommended by the Food and Agricultural Organization/World Health Organization (FAO/WHO). Moreover, their concentrations in foods containing Monascus differ widely for different food varieties, suggesting that external contaminants and raw materials are the main sources of trace elements. This study shows that ICP-MS is a simple method proposed for the determination of As, Cd, Cr, Pb, Se, Cu, and Zn in foods containing Monascus.

Survey of total mercury in foods from Taiwan containing red mould rice (Monascus) using a direct mercury analyser (DMA).

Total mercury concentrations in 69 red mould rice (Monascus) food samples purchased in Taipei, Taiwan, were determined using the direct mercury analyser (DMA) method. The highest mean levels of total mercury in these samples were observed in samples of canned roast eel (20 µg kg(-1)), soy fibrous product (14 µg kg(-1)), red mould rice (8.5 µg kg(-1)), cereal (7.6 µg kg(-1)), dried pork fibre (7.5 µg kg(-1)), and dietary supplement (7.2 µg kg(-1)). All samples analysed had mercury levels below the limit of 50 µg kg(-1) for food standards in rice, edible oil, and fat of Taiwan. The mercury concentration in the Monascus foods differed widely between different food varieties, suggesting that external contamination and raw materials are the main sources of mercury. This study shows that DMA is a simple method proposed for the determination of total mercury in foods containing Monascus. The method requires no sample pre-treatment, and it minimizes potential sources of contamination. The data (42±2 µg kg(-1)) obtained from five analyses of a standard reference material (apple leaves, NIST-1515) showed good agreement with the certified reference value (44±4 µg kg(-1)) provided by the US National Institute of Standards and Technology (NIST). The precision based on the analysis of standard reference material was 4.1%; the average recovery was 95%.

Clinical significance of cell differentiation in hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma is commonly found in Asian countries and prognosis still remains unsatisfactory due to recurrence after surgical tumor resection. METHODOLOGY: We try to demonstrate the recurrence and survival time in 99 surgical patients grading by tumor cellular differentiation from surgical specimen. RESULTS: The rates of well, moderate, and poor differentiation were encountered in 21 cases (21.2%), 61 cases (61.6%) and 17 cases (17.7%), respectively. Small tumor (< 3 cm) was found in only one (5.9%) in the poor differentiation group and 38.1% and 37.7% in the well and moderate differentiation groups. Capsular invasion was found in 13 (61.9%), 39 (63.9%) and 7 (41.1%) in the well, moderate and poor differentiation group, respectively. We found 41.9% (18/43) and 22.4% (13/58) to be tumor free in capsule invasion (-) and (+) after a period of 18.1 and 29.9 months, respectively. However, the recurrent time was 10.6 and 11.3 months, respectively with no significant difference (p > 0.05). Vascular invasion was more frequent in the poor differentiation group (76.5%) than the well (23.8%) and moderate (60.7%) differentiation groups (P < 0.05). We found 23.5% (4/17) and 35% (21/60) to be tumor free but the recurrence time was 6.5 and 14.1 months for the vascular invasion (-) and (+), respectively. The residual median survival times were 6.5 and 14 months after recurrence, respectively. The tumor recurrence rates were 52.7% (11/21), 52.4% (32/61), and 35.5% (6/17) and recurrence times were 11.7, 11.9, and 4.5 months for the well, moderate and poor differentiation group respectively totally. The recurrence time of young age group (< 39 years old) was shorter than the others and there was no patient of well differentiation less than 40 years old. The recurrence time was shorter in the poor differentiation group but there was no significant difference according to age group. The median survival times were 22.2, 22.9, and 9.5 months for each group, respectively. CONCLUSIONS: Differentiation of hepatocellular carcinoma cell had a clinical significance and was found to be positively correlated with the invasive proclivity. The median survival time was longer in both the well and moderate differentiation group, but not in the poor differentiation group. The clinical data revealed that the extended operations performed upon the patients with poor differentiation effected the recurrence time but not the survival time.

beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass.

Regulation of glucose homeostasis by insulin depends on the maintenance of normal beta-cell mass and function. Insulin-like growth factor 1 (Igf1) has been implicated in islet development and differentiated function, but the factors controlling this process are poorly understood. Pancreatic islets produce Igf1 and Igf2, which bind to specific receptors on beta-cells. Igf1 has been shown to influence beta-cell apoptosis, and both Igf1 and Igf2 increase islet growth; Igf2 does so in a manner additive with fibroblast growth factor 2 (ref. 10). When mice deficient for the Igf1 receptor (Igf1r(+/-)) are bred with mice lacking insulin receptor substrate 2 (Irs2(-/-)), the resulting compound knockout mice show a reduction in mass of beta-cells similar to that observed in pancreas of Igf1r(-/-) mice (ref. 11), suggesting a role for Igf1r in growth of beta-cells. It is possible, however, that the effects in these mice occur secondary to changes in vascular endothelium or in the pancreatic ductal cells, or because of a decrease in the effects of other hormones implicated in islet growth. To directly define the role of Igf1, we have created a mouse with a beta-cell-specific knockout of Igf1r (betaIgf1r(-/-)). These mice show normal growth and development of beta-cells, but have reduced expression of Slc2a2 (also known as Glut2) and Gck (encoding glucokinase) in beta-cells, which results in defective glucose-stimulated insulin secretion and impaired glucose tolerance. Thus, Igf1r is not crucial for islet beta-cell development, but participates in control of differentiated function.

Vitreous-induced modulation of integrins in retinal pigment epithelial cells: effects of fibroblast growth factor-2.

Growth in the presence of vitreous results in transformation of human RPE cells from an epithelioid to a fibroblast-like appearance and leads to an elevation of the expression of alpha(5) and alpha(2) integrins, while the level of alpha(3) integrin is reduced. These changes are inhibited by the presence of FGF-2. Vitreous treatment increases mobility, as does antibody neutralization of FGF-2 or antibody blockade of FGF receptors. The vitreous-induced rise in mobility depends on an increase in alpha(5) integrin expression since it is inhibited by anti-alpha(5) integrin antibodies. Expression of alpha(5) integrin as a result of infection of RPE cells with an alpha(5) integrin-encoding adenovirus induced morphological transformation and an increase in mobility similar to that seen with vitreous. It is concluded that a decrease in FGF-2 plays an important role in vitreous-induced alterations of RPE cell morphology, integrin expression and mobility. High FGF-2 levels prevent at least some of the increased mobility of RPE cells induced by vitreous. This is mediated via extracellular FGF-2 binding to FGF receptor(s) since antibodies to FGF-2 or to its receptor(s) mimic the effects of vitreous. Changes in mobility and morphology involve altered alpha(5) integrin expression since mobility is blocked by antibodies against these proteins while elevated alpha(5) integrin expression increases mobility and leads to morphological changes.

The role of high-density lipoproteins in oxidation and inflammation.

High-density lipoproteins (HDL) in the basal state are anti-inflammatory, capable of destroying oxidized lipids that generate an inflammatory response. However, HDL during acute inflammation are altered and become pro-inflammatory. This "chameleon-like" nature of HDL is considered to be due to the complex composition of HDL. The data reviewed here demonstrate the key role of HDL in modulating inflammation and its implications for atherogenesis.