Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found in 35 and 30 % of US adults, respectively. Trans-10, cis-12-conjugated linoleic acid (CLA) has been found to cause both these disorders in several animal models. We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed either a control diet or diets containing trans-10, cis-12-CLA (0.5 %) or CLA+flaxseed oil (FSO)(0.5 %+0.5 %) for 8 weeks. Weights of livers, concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for IR and HOMA1 for beta cell function were higher by 160, 636, 985 and 968 % in the CLA group compared with those in the control group. FSO decreased fasting glucose by 20 % and liver weights by 37 % compared with those in the CLA group; it maintained circulating insulin, HOMA1-IR and HOMA1 for beta cell function at levels found in the control group. CLA supplementation decreased n-6 and n-3 wt% concentrations of liver lipids by 57 and 73 % and increased the n-6:n-3 ratio by 58 % compared with corresponding values in the control group. FSO increased n-6 and n-3 PUFA in liver lipids by 33 and 342 % and decreased the n-6:n-3 ratio by 70 % compared with corresponding values in the CLA group. The present results suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and that these can be corrected by a concomitant increase in the intake of alpha-linolenic acid, 18 : 3n-3.

Abstract Background: Concomitant supplementation of 1.5% docosahexaenoic acid (22:6 n-3; DHA) with 0.5% t10, c12-conjugated linoleic acid (18:2 n-6; CLA) prevented the CLA-induced increase in expression of hepatic genes involved in fatty acid synthesis and the decrease in expression of genes involved in fatty acid oxidation. The effect of CLA on fatty acid compositions of adipose tissue and muscle and whether DHA can prevent those CLA-induced changes in fatty acid composition is not known. Methods: We investigated if DHA fed concomitantly with CLA for 4 weeks will prevent the CLA-induced changes in fatty acid compositions of liver, adipose, and muscle lipids in C57BL/6N female mice. We also examined changes in expression of adipose tissue genes involved in fatty acid synthesis, oxidation, uptake, and lipolysis. Results: CLA supplementation increased liver fat and decreased total n-3 polyunsaturated fat (PUFA) concentration. DHA not only prevented the CLA-induced changes in liver fat, but also increased n-3 PUFA by >350% as compared with the control group. CLA decreased adipose weight and the expression of genes involved in fatty acid synthesis, oxidation, and uptake and increased that of uncoupling protein 2 (UCP2). Supplementing DHA along with CLA increased adipose n-3 PUFA by >1000% compared with control group, but did not prevent the CLA-induced changes in mass or gene expression. Both CLA and DHA were incorporated into muscle lipids, but had minor effects on fatty acid composition. Conclusions: Liver, adipose tissue, and muscle responded differently to CLA and DHA supplementation. DHA prevented CLA-induced increase in liver fat but not loss of adipose mass.

We have reviewed effects of long chain (LC) n-3 PUFA on markers of atherosclerosis in human subjects with a focus on individual effects of EPA and DHA. Initial results from epidemiological studies suggested that LC n-3 PUFA from fish oils (FO) reduced incidence of CVD; those results have been confirmed in interventional studies. Dietary intervention with n-3 PUFA decreased fasting and postprandial TAG, number of remnant-like chylomicron particles, large VLDL, and total and small dense LDL particles. It increased mean size of LDL particles by increasing number of large and decreasing those of small dense particles. With some exceptions, n-3 PUFA decreased blood pressure (BP) and heart rate (HR), flow-mediated dilation (FMD) and plasma concentrations of inflammatory markers. n-3 PUFA also decreased circulating adhesion molecules and intima-media thickness (IMT) in some but not other studies. For IMT, results varied with the sex and artery being examined. EPA effects on FMD are endothelial cell dependent, while those of DHA seem to be endothelial cell independent. Individually, both EPA and DHA decreased TAG and inflammatory markers, but only DHA decreased HR, BP and number of small dense LDL particles. Results varied because of dose and duration of n-3 PUFA, EPA:DHA, health status of subjects and other reasons. Future studies are needed to determine optimal doses of EPA and DHA individually, their synergistic, additive or antagonistic effects, and to understand underlying mechanisms. In conclusion, n-3 PUFA decreased several risk factors for atherosclerosis without any serious adverse effects.

Abstract Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented trans-10, cis-12-conjugated linoleic acid (CLA)-induced nonalcoholic fatty liver disease (NAFLD) and insulin resistance. The effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined the ability of DHA (0.5% and 1.5%) to prevent increases in NAFLD and homeostatic model assessment of insulin resistance (HOMA-IR) induced by CLA (0.5%) when fed concomitantly for 4 weeks to C57BL/6N female mice. We also examined changes in expression of hepatic genes involved in fatty acid synthesis and oxidation. Results: CLA supplementation increased liver triglycerides (TG) and HOMA-IR by 221% and 547%, respectively, and decreased mass of different adipose depots by 65%-90% when compared to those in the control group. When fed concomitantly, DHA prevented CLA-induced increases in liver TG and circulating insulin with varying efficiency, but it did not prevent loss in adipose tissue mass. In the CLA+0.5% DHA group, the liver TG did not differ from those in the control group, but circulating insulin and HOMA-IR were 285% and 264%, respectively. In the CLA+1.5% DHA group, liver TG were 54% lower than those in the control group, but circulating insulin concentration and HOMA-IR did not differ between these two groups. CLA increased the expression of hepatic genes involved in fatty acid synthesis and decreased the expression of genes involved in fatty acid oxidation, and 1.5% DHA prevented changes in the expression of hepatic genes caused by CLA. Conclusions: Response of different tissues to CLA and DHA varied; CLA was more potent than DHA in altering depot fat and insulin concentrations.

BACKGROUND Increase in obesity and metabolic syndrome are associated with increases in insulin resistance (IR) and type 2 diabetes mellitus. Results from animal intervention studies and human epidemiological studies suggest that n-3 polyunsaturated fatty acids can prevent and reverse IR, but results from human intervention studies have varied. Results from some human and animal studies suggest that docosahexaenoic acid (22:6n-3; DHA) may be more effective than eicosapentaenoic acid (20:5n-3; EPA) in the prevention of IR. METHODS By using a placebo-controlled, parallel study design, we examined the effects of DHA supplementation (3 grams/day, 90 days) in the absence of EPA on glucocentric and lipocentric markers of IR in hypertriglyceridemic men (n=14-17/group). RESULTS DHA supplementation increased fasting plasma glucose concentration by 4.7%(P<0.05), but did not alter other indices of IR based on fasting (insulin and homeostasis model assessment of insulin resistance [HOMA-IR]) or postprandial insulin and glucose concentrations (areas under curves for insulin and glucose, Matsuda index). Glucose increased by 2.7% in the placebo group and was not significant; increases in glucose in the two groups did not differ from each other. DHA decreased circulating concentrations of several lipocentric markers of IR, including plasma concentrations of nonesterified fatty acids (13.0%), small, dense low-density lipoprotein (LDL) particles (21.7%), and ratio of tryglycerides to high-density lipoprotein cholesterol (TG/HDL-C)(34.0%)(P<0.05). None of the variables changed in the placebo group. CONCLUSIONS Our results suggest that lipocentric markers of IR are more responsive to DHA supplementation than the glucocentric markers. Future studies with DHA in prediabetic subjects and direct measures of insulin sensitivity are needed.

Emerging evidence reveals that pattern-recognition receptors (PRRs), Toll-like receptors (TLRs), and nucleotide-binding oligomerization domain proteins (NODs) mediate both infection-induced and sterile inflammation by recognizing pathogen-associated molecular patterns and endogenous molecules, respectively. PRR-mediated chronic inflammation is a determinant for the development and progression of chronic diseases including cancer, atherosclerosis, and insulin resistance. Recent studies demonstrated that certain phytochemicals inhibit PRR-mediated pro-inflammation. Curcumin, helenalin, and cinnamaldehyde with α, β-unsaturated carbonyl groups, or sulforaphane with an isothiocyanate group, inhibit TLR4 activation by interfering with cysteine residue-mediated receptor dimerization, while resveratrol, with no unsaturated carbonyl group, did not. Similarly, curcumin, parthenolide, and helenalin, but not resveratrol and (-)-epigallocatechin-3-gallate (EGCG), also inhibit NOD2 activation by interfering with NOD2 dimerization. In contrast, resveratrol, EGCG, luteolin, and structural analogs of luteolin specifically inhibit TLR3 and TLR4 signaling by targeting TANK binding kinase 1 (TBK1) and receptor interacting protein 1 (RIP1) in Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) complex. Together, these results suggest that PRRs and downstream signaling components are molecular targets for dietary strategies to reduce PRR-mediated chronic inflammation and consequent risks of chronic diseases.

The chemopreventive properties of the chromatin-binding soy peptide, lunasin, are well documented, but its mechanism of action is unclear. To elucidate the mechanism by which lunasin reduces tumor foci formation in cultured mammalian cells, nontumorigenic (RWPE-1) and tumorigenic (RWPE-2) human prostate epithelial cells were treated with lunasin followed by gene expression profiling and characterization of the chromatin acetylation status for certain chemopreventive genes. The genes HIF1A, PRKAR1A, TOB1, and THBS1 were upregulated by lunasin in RWPE-1 but not in RWPE-2 cells. Using histone acetyltransferase (HAT) assays with acid-extracted histones as templates, we showed that lunasin specifically inhibited H4K8 acetylation while enhanced H4K16 acetylation catalyzed by HAT enzymes p300, PCAF, and HAT1A. These results suggest a novel mechanism for lunasin-dependent upregulation of gene expression. Chromatin immunoprecipitation (ChIP) revealed hypoacetylation of H4K16 in RWPE-2 cells, specifically at the 5' end of THBS1 containing a CpG island. Moreover, bisulfite PCR (BSP) and subsequent DNA sequencing indicated that this CpG island was hypomethylated in RWPE-1 but hypermethylated in RWPE-2 cells. Histone hypoacetylation and DNA hypermethylation in the 5' region of THBS1 may explain the inability of lunasin to upregulate this gene in RWPE-2 cells.

Vitamin C is a strong antioxidant that alters gene expression in cells, and its effects can be modified by cellular oxidative stress. We investigated the genome-wide effects of vitamin C on the in vivo transcriptome in the liver, which synthesizes various enzymes and proteins to defend against cellular oxidative stress. We fed mice vitamin C (0.056 mg/g of body weight) for 1 week and performed DNA microarray analysis with hepatic mRNA in fasting and refeeding states to mimic physiological conditions of oxidative stress. Significance analysis of microarray data identified approximately 6,000 genes differentially expressed in both fasting and refeeding states. In the fasting state, vitamin C induced overall energy metabolism as well as radical scavenging pathways. These were ameliorated in the refeeding state. These findings suggest that vitamin C has profound and immediate global effects on hepatic gene expression, which may help prevent oxidative stress, and that long-term treatment with vitamin C might reduce the risk of chronic disease.

Typical omega 3 polyunsaturated fatty acids (n-3 PUFAs) are docosahexaenoic acid and eicosapentaenoic acid in the form of fish oils and alpha linolenic acid from flaxseed oil. Epidemiological studies suggested the benefits of n-3 PUFA on cardiovascular health. Intervention studies confirmed that the consumption of n-3 PUFA provided benefits for primary and secondary prevention of cardiovascular disease. Evidence from cellular and molecular research studies indicates that the cardioprotective effects of n-3 PUFA result from a synergism between multiple, intricate mechanisms that involve antiinflammation, proresolving lipid mediators, modulation of cardiac ion channels, reduction of triglycerides, influence on membrane microdomains and downstream cell signaling pathways and antithrombotic and antiarrhythmic effects. n-3 PUFAs inhibit inflammatory signaling pathways (nuclear factor-kappa B activity) and down-regulate fatty acid (FA) synthesis gene expression (sterol regulatory element binding protein-1c) and up-regulate gene expression involved in FA oxidation (peroxisome proliferator-activated receptor alpha). This review examines the various mechanisms by which n-3 PUFA exert beneficial effects against CVD.

Chronic inflammation is known to promote the development of many chronic diseases. Pattern recognition receptors (PRRs), Toll-like receptors (TLRs), and nucleotide-binding oligomerization domain proteins (NODs) mediate both infection-induced inflammation and sterile inflammation by recognizing pathogen- associated molecular patterns and endogenous molecules, respectively. PRR-mediated inflammation is an important determinant in altering the risk of many chronic diseases. Saturated fatty acids (SFAs) can activate PRRs, leading to enhanced expression of pro-inflammatory target gene products. However, n-3 polyunsaturated fatty acids (PUFAs) inhibit agonist-induced activation of PRRs. These results suggest that SFAs and n-3 PUFAs can reciprocally modulate PRR-mediated inflammation, and that PRRs and their downstream signaling components are molecular targets for dietary strategies to reduce chronic inflammation and subsequent risk of chronic diseases. This advancement in knowledge provides a new paradigm for understanding the mechanism by which different dietary fatty acids modify risk of chronic diseases including insulin resistance, atherosclerosis, and cancer.

The importance of the lectin-like oxidized LDL receptor (LOX-1) gene in cardiovascular and other diseases is slowly being revealed. LOX-1 gene expression appears to be a "canary in a coal mine" for atherogenesis, being strongly up-regulated early on in a number of cell types when they are activated, and predicting the sites of future disease. From this early time point the LOX-1 protein often participates in the disease process itself. While gene/protein expression can be regulated on a multiplicity of levels, the most basic and important mode of regulation is usually transcriptional. There are very few studies on the transcriptional regulation of the human LOX-1 promoter; fewer still on definitive mapping of the transcription factors involved. It is known that a wide variety of stimuli up-regulate LOX-1, usually/probably on the transcriptional level. Angiotensin II (Ang II) is one important regulator of renin-angiotensin system and stimulator LOX-1. Ang II is known to up-regulate LOX-1 transcription through an NF-kB motif located at nt -2158. Oxidized low density lipoprotein (ox-LDL) is another important cardiovascular regulator, particularly of atherosclerotic disease, and a strong stimulator of LOX-1. Ox-LDL is known to up-regulate LOX-1 transcription through an Oct-1 motif located at nt -1556. The subsequent enhanced LOX-1 receptor numbers and their binding by ox-LDL ligand triggers a positive feedback loop, increasing further LOX-1 expression, with a presently unknown regulatory governor. The Oct-1 gene also has its own Oct-1-driven positive feedback loop, which likely also contributes to LOX-1 up-regulation. There is also data which suggests the involvement of the transcription factor AP-1 during stimulation with Phorbol 12-myristate acetate. While the importance of NF-κB as a transcriptional regulator of cardiovascular-relevant genes is well known, the importance of Oct-1 is not. Data suggests that Oct-1-mediated up-regulation of transcription is an early event in the stimulation of LOX-1 by ox-LDL. Yet Oct-1 also down-regulates cardiovascular-relevant genes by suppressing NF-κB transactivation. Thus, Oct-1 is presently somewhat of an enigma, up-regulating and down-regulating genes seemingly at random without an overall theme (with the exception of cell cycle). Yet the up-regulation of LOX-1 by ox-LDL is a very important event in atherogenesis (both early and late) and Oct-1 is, therefore, an important transcriptional gatekeeper of this important atherogenic trigger.

BACKGROUND Dietary fish-oil supplementation has been shown in human kinetic studies to lower the production rate of apolipoprotein (apo) A-I, the major protein component of HDL. The underlying mechanism responsible for this effect is not fully understood. OBJECTIVE We investigated the effect and the mechanism of action of the very-long-chain n-3 (omega-3) polyunsaturated fatty acid docosahexaenoic acid (DHA), relative to the saturated fatty acid palmitic acid (PA), on the hepatic expression of apo A-I in HepG2 cells. DESIGN HepG2 cells were treated with different doses of DHA and PA (0-200 μmol/L). mRNA expression levels of apo A-I were assessed by real-time polymerase chain reaction, and apo A-I protein concentrations were measured by immunoassay. DHA dose-dependently suppressed apo A-I mRNA levels and also lowered apo A-I protein concentrations in the media, with maximum effects at 200 μmol/L. This concentration of fatty acids was used in all subsequent experiments. RESULTS To elucidate the mechanism mediating the reduction in apo A-I expression by DHA, transfection experiments were conducted with plasmid constructs containing serial deletions of the apo A-I promoter. The DHA-responsive region was mapped to the -185 to -148 nucleotide region of the apo A-I promoter, which binds the hepatocyte nuclear factor (HNF)-3β. Nuclear extracts from cells treated with DHA or PA had a similar nuclear abundance of HNF-3β. However, electrophoresis mobility shift assays showed less binding of HNF-3β to the -180 to -140 sequence of the apo A-I promoter than did PA-treated cells. As shown by chromatin immunoprecipitation analysis, less HNF-3β was recruited to the apo A-I promoter in DHA-treated cells than in PA-treated cells, which supports the concept of an interference of DHA with the binding of HNF-3β to the apo A-I promoter. CONCLUSION These findings suggest that, in human hepatoma HepG2 cells, DHA inhibits the binding of HNF-3β to the apo A-I promoter, resulting in the repression of apo A-I promoter transactivity and thus a reduction in apo A-I expression.

Fe(3)O(4) magnetic nanoparticles (MNPs) coated with 2,3-dimercaptosuccinnic acid (DMSA) are considered to be a promising nanomaterial with biocompatibility. In the present study, the effects of DMSA-coated Fe(3)O(4) MNPs on the expression of all identified mouse genes, which regulate various cellular biological processes, were determined to establish whether this nanoparticle is cytotoxic to mammalian cells. Mouse macrophage RAW264.7 cells were treated with 100μg/ml of DMSA-coated Fe(3)O(4) MNPs for 4, 24 and 48h, and the global gene expression was detected via Affymetrix Mouse Genome 430 2.0 GeneChips(®) microarrays. It was found that gene expression of 711, 545 and 434 transcripts was significantly altered by 4-, 24- and 48-h treatments, respectively. Of these genes, 27 were consistently upregulated and 6 were consistently downregulated at the three treatment durations. Bioinformatic analysis of all differentially expressed genes revealed that this nanoparticle can strongly activate inflammatory and immune responses and can inhibit the biosynthesis and metabolism of RAW264.7 cells at a dose of 100μg/ml. These results demonstrated that DMSA-coated Fe(3)O(4) MNPs display cytotoxicity in this type of macrophage at high doses.

Endothelial cells (ECs) apoptosis induced by oxidized low-density lipoprotein (ox-LDL) is thought to play a critical role in atherosclerosis. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. However, whether miRNAs are associated with ox-LDL induced apoptosis and their effect on ECs is still unknown. Therefore, this study evaluated potential miRNAs and their involvement in ECs apoptosis in response to ox-LDL stimulation. Microarray and qRT-PCR analysis performed on human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL identified 15 differentially expressed (4 up- and 11 down-regulated) miRNAs. Web-based query tools were utilized to predict the target genes of the differentially expressed miRNAs, and the potential target genes were classified into different function categories with the gene ontology (GO) term and KEGG pathway annotation. In particular, bioinformatics analysis suggested that anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2) is a target gene of miR-365, an apoptomir up-regulated by ox-LDL stimulation in HUVECs. We further showed that transfection of miR-365 inhibitor partly restored Bcl-2 expression at both mRNA and protein levels, leading to a reduction of ox-LDL-mediated apoptosis in HUVECs. Taken together, our findings indicate that miRNAs participate in ox-LDL-mediated apoptosis in HUVECs. MiR-365 potentiates ox-LDL-induced ECs apoptosis by regulating the expression of Bcl-2, suggesting potential novel therapeutic targets for atherosclerosis.

H(2) is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. LOX-1 expression can be upregulated by various stimuli, including TNF-α. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked by H(2) in endothelial cells. H(2) significantly abolished the upregulation of LOX-1 by different stimuli, including TNF-α, at the protein and mRNA levels. The TNF-α-induced upregulation of LOX-1 was also attenuated by the NF-κB inhibitor N-acetyl-L-cysteine. H(2) inhibited the TNF-α-induced activation of NF-κB and the phosphorylation of IκB-α. Furthermore, H(2) inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H(2) probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation.

Aim: Increased levels of small dense low-density lipoproteins (sd-LDL) have been reported more atherogenic compared to total low-density lipoprotein (LDL); however, no definitive experiments using macrophages have examined this concept in vitro.Method and Result: In this study, we isolated fractions of total LDL (density 1.019-1.063g/ml) and sd-LDL (density 1.044-1.063g/ml) from the plasma of subjects with modest hypertriglycidemia. Oxidizabilty as assessed by copper-induced generation (1.6 µmol/L CuSO(4),12 h) of thiobarbituric acid reactive substances (TBARS) was significantly greater (7-fold higher, p < 0.01) for sd-LDL (4.3±1.1 nmol/mg) than for total LDL (0.6±0.2 nmol/mg) at the same cholesterol concentrations. Moreover, oxidized sd-LDL induced more lipid staining in macrophages than oxidized total LDL. When non-oxidized sd-LDL were incubated with THP1 macrophages, there was much greater lipid accumulation as assessed by oil red O staining, and more than a 2-fold increase (p < 0.05) in intracellular triglyceride content as compared to non-oxidized total LDL. Furthermore, non-oxidized sd-LDL in contrast to non-oxidized total LDL enhanced macrophage lectin-like oxidized LDL receptor-1 (LOX-1) protein expression and significantly LOX-1 mRNA levels (+158%, p < 0.05), with no effect on scavenger receptor A or CD36 gene expression. These effects of non-oxidized sd-LDL on LOX-1 gene expression were suppressed when Toll-like receptor 4 was inactivated either by RNAi or antibody.Conclusion: Our data indicate for the first time that sd-LDL is much more effective in promoting macrophage triglyceride accumulation and LOX-1 gene expression than total LDL.

Gene expression signatures in blood correlate with specific diseases. Such signatures may serve as valuable diagnostic and prognostic tools in disease management. Blood gene expression signatures associated with heart failure may be applied to predict prognosis, monitor disease progression, and optimize treatment. Blood gene expression profiles were generated for 71 subjects with heart failure and 15 controls without heart failure, using the Affymetrix GeneChip U133Plus2.0. Survival analysis identified 197 "mortality genes" that were significantly associated with patient outcome. Functional categorization showed that genes associated with T cell receptor signaling were most significantly overpresented. Cluster analysis of these T cell receptor signaling genes significantly categorized heart failure patients into three risk groups (P = 0.031) that were distinct from the three risk groups categorized by New York Heart Association (NYHA) Classification (P = 0.0002). By combining the analysis of clinical assessment (NYHA class) with T cell receptor signaling gene expression, we proposed a model that demonstrated an even greater differentiation of patients at risk (P = 0.0001). In this discovery study, we identified blood expression signatures associated with heart failure patient outcomes. Characterization of these mortality genes helped identify a set of T cell receptor signaling genes that may be of utility in predicting survival of heart failure patients. These data raise the possibility of prospectively risk stratifying patients with heart failure by integrating blood gene expression signatures with current clinical assessment.

HASH(0x1f9861f0)

To clarify the difference between gene expression signature of Epstein-Barr virus (EBV)-positive gammadelta T-cell lymphoproliferative disorders (LPD) and those in normal gammadelta T-cells, we set out to determine gene expression profiling using three gammadelta T-cell lines derived from patients with EBV-positive gammadelta T-cell LPD. Gene expression profiling using an Affymetrix Genechip revealed a unique gene expression pattern of NK cell receptors in gammadelta T-LPD cell lines. Genes encoding killer cell lectin-like receptors (KLR), such as KLRG1 and KLRB1 (CD161), were generally low in gammadelta T-LPD cell lines, while killer cell immunoglobulin-like receptors varied among cell lines. In addition, expression of CD161 surface antigen was found to be remarkably decreased in gammadelta T-LPD cell lines by flow cytometric analysis. We conclude that gammadelta T-cell expansion in EBV-positive gammadelta T-LPD is in part due to inappropriate expression of the NK cell receptors which related to impaired function cytotoxic T cells.

BACKGROUND: Human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, OLR1) has been identified as a cell surface endocytosis receptor for oxidized low-density lipoprotein (oxLDL) on vascular endothelial cells. OxLDLs are avidly ingested by macrophages, resulting in foam cell formation. OxLDLs are also involved in inducing smooth muscle cell migration, proliferation and transformation. A single nucleotide polymorphism K167N (G501C) of the LOX-1 gene results in an amino acid dimorphism (Lys/Asn) at residue 167. Replacement of this Lys residue causes reduced binding and internalization of oxLDL. The purpose of this study was to investigate the effect of the LOX-1 K167N gene polymorphism in Turkish patients with coronary artery disease (CAD). MATERIALS AND METHODS: K167N polymorphism were studied in 91 patients with CAD and 72 healthy controls by the PCR-RFLP method. RESULTS: The frequencies of the KK genotype and the K allele were higher in the CAD group than the controls (p<0.05), while the frequency of the NN genotype was higher in the control group than in the CAD group (p<0.05). It was observed that the decreased CAD risk in patients who had the N allele was reversed by male sex (OR: 0.400 -->0.481) and smoking (OR: 0.400 -->0.949). Although male sex and smoking were lower than other cardiovascular risk factors in patients with the N allele they were higher than other cardiovascular risk factors in patients with the K allele. CONCLUSION: Male sex and smoking decrease the protective effects of the N allele. The adverse effects of the K allele on the CAD risk resulting from the K167N polymorphism appear to be independent of other cardiovascular risk factors.