The anti-atherogenic effects of eicosapentaenoic and docosahexaenoic acid are dependent on the stage of THP-1 macrophage differentiation.

In this study LC n-3 PUFA-specific effects on the degree of monocyte differentiation and macrophage foam cell formation were investigated by treating PMA-induced immature and mature macrophage models with LC n-3/n-6 PUFA during and post-differentiation. During immature macrophage differentiation LC n-3 PUFA alone decreased TNFα mRNA levels. EPA, and the n-6 PUFAs, linoleic acid and arachidonic acid, decreased CD36 mRNA levels, and EPA also downregulated CD49d cell-surface expression. Both LC n-3 PUFA reduced LDLr mRNA levels in immature macrophages, while DHA alone reduced levels in mature macrophages. Post-differentiation, n-3 and -6 PUFA reduced basal, but not oxidised LDL dependent cholesterol levels in immature macrophages. LC n-3 PUFA-specific reductions in LDLr and LOX-1 mRNA expression were also observed.

This study found LC n-3 PUFA specific, anti-atherogenic effects were more significant in immature macrophages. LC n-3 PUFA effects may be modulated by the extent of monocyte to macrophage differentiation.

Antioxidant and anti-atherogenic activities of olive oil phenolics

The aim of the current study was to investigate the antioxidant and cellular activity of the olive oil phenolics oleuropein, tyrosol, hydroxytyrosol, and homovanillic alcohol (which is also a major metabolite of hydroxytyrosol). Well-characterized chemical and biochemical assays were used to assess the antioxidant potential of the compounds. Further experiments investigated their influence in cell culture on cytotoxic effects of hydrogen peroxide and oxidized low-density lipoprotein (LDL), nitric oxide production by activated macrophages, and secretion of chemoattractant and cell adhesion molecules by the endothelium. Inhibitory influences on in vitro platelet aggregation were also measured. The antioxidant assays indicated that homovanillic alcohol was a significantly more potent antioxidant than the other phenolics, both in chemical assays and in prolonging the lag phase of LDL oxidation. Cell culture experiments suggested that the olive oil phenolics induce a significant reduction in the secretion of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (and a trend towards a reduced secretion of monocyte chemoattractant protein-1), and protect against cytotoxic effects of hydrogen peroxide and oxidized LDL. However, no influence on nitric oxide production or platelet aggregation was evident. The data show that olive oil phenolics have biochemical and cellular actions, which, if also apparent in vivo, could exert cardioprotective effects.

Antioxidant and anti-atherogenic activities of olive oil phenolics

The aim of the current study was to investigate the antioxidant and cellular activity of the olive oil phenolics oleuropein, tyrosol, hydroxytyrosol, and homovanillic alcohol (which is also a major metabolite of hydroxytyrosol). Well-characterized chemical and biochemical assays were used to assess the antioxidant potential of the compounds. Further experiments investigated their influence in cell culture on cytotoxic effects of hydrogen peroxide and oxidized low-density lipoprotein (LDL), nitric oxide production by activated macrophages, and secretion of chemoattractant and cell adhesion molecules by the endothelium. Inhibitory influences on in vitro platelet aggregation were also measured. The antioxidant assays indicated that homovanillic alcohol was a significantly more potent antioxidant than the other phenolics, both in chemical assays and in prolonging the lag phase of LDL oxidation. Cell culture experiments suggested that the olive oil phenolics induce a significant reduction in the secretion of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (and a trend towards a reduced secretion of monocyte chemoattractant protein-1), and protect against cytotoxic effects of hydrogen peroxide and oxidized LDL. However, no influence on nitric oxide production or platelet aggregation was evident. The data show that olive oil phenolics have biochemical and cellular actions, which, if also apparent in vivo, could exert cardioprotective effects.

Dietary long-chain n-3 PUFAs increase LPL gene expression in adipose tissue of subjects with an atherogenic lipoprotein phenotype

We sought to test the hypothesis that dietary long-chain n-3 PUFA (LC n-3 PUFA) in fish oil stimulate the gene expression of lipoprotein lipase (LPL) in human adipose tissue (AT). In a randomized, double blind, placebo-controlled, cross-over study, 51 male subjects expressing an atherogenic lipoprotein phenotype (ALP) had their diets supplemented with fish oil for 6 weeks. As we previously reported for this group, supplementation with LC n-3 PUFA produced a decrease in fasting plasma triglyceride (TG) (−35%, P < 0.05), attenuation of the postprandial TG response (area and incremental area under the curve; AUC and IAUC, P < 0.05), and a decrease in small, dense LDL. The present study extended these observations by showing that these changes were accompanied by a marked increase in the concentration of LPL mRNA in adipose tissue (AT-LPL mRNA, +55%, P = 0.003) and post-heparin LPL activity (PH-LPL, +31%, P = 0.036). There was also evidence of an association between LPL gene expression and polymorphism in the apolipoprotein E gene. We conclude that the favorable influence of dietary n-3 PUFA on the ALP may be mediated, in part, through an increase in the plasma activity and gene expression of lipoprotein lipase in human adipose tissue.

Modest doses of beta-glucan do not reduce concentrations of potentially atherogenic lipoproteins

BACKGROUND: In 1997, the US Food and Drug Administration passed a unique ruling that allowed oat bran to be registered as the first cholesterol-reducing food at a dosage of 3 g beta-glucan/d. OBJECTIVE: The effects of a low dose of oat bran in the background diet only were investigated in volunteers with mild-to-moderate hyperlipidemia. DESIGN: The study was a double-blind, placebo-controlled, randomized, parallel study. Sixty-two healthy men (n = 31) and women (n = 31) were randomly allocated to consume either 20 g oat bran concentrate (OBC; containing 3 g beta-glucan) or 20 g wheat bran (control) daily for 8 wk. Fasting blood samples were collected at weeks -1, 0, 4, 8, and 12. A subgroup (n = 17) was studied postprandially after consumption of 2 meals (containing no OBC or wheat bran) at baseline and after supplementation. Fasting plasma samples were analyzed for total cholesterol, HDL cholesterol, triacylglycerol, glucose, and insulin. LDL cholesterol was measured by using the Friedewald formula. The postprandial samples were anlayzed for triacylglycerol, glucose, and insulin. RESULTS: No significant difference was observed in fasting plasma cholesterol, LDL cholesterol, glucose, or insulin between the OBC and wheat-bran groups. HDL-cholesterol concentrations fell significantly from weeks 0 to 8 in the OBC group (P = 0.05). There was a significant increase in fasting glucose concentrations after both OBC (P = 0.03) and wheat-bran (P = 0.02) consumption. No significant difference was found between the OBC and wheat-bran groups in any of the postprandial variables measured. CONCLUSIONS: A low dosage of beta-glucan (3 g/d) did not significantly reduce total cholesterol or LDL cholesterol in volunteers with plasma cholesterol concentrations representative of a middle-aged UK population.

Lack of association between lipaemia and central adiposity in subjects with an atherogenic lipoprotein phenotype (ALP)

OBJECTIVE: To investigate the associations between indices of adiposity and cardiovascular risk factors in individuals with an atherogenic lipoprotein phenotype (ALP). SUBJECTS: Fifty-five men, aged 34-69 y, body mass index (BMI) 22-35 kg/m2, with an ALP lipid profile (triglycerides (TG) 1.5-4.0 mmol/l, HDL<1.1 mmol/l; %LDL-3>40% total LDL). DESIGN: Each participant provided a fasting blood sample and underwent an 8 h postprandial assessment and had anthropometric measurements taken. OUTCOME MEASURES: BMI, waist circumference (W), waist-to-hip ratio (W/H), sum of skinfolds (SSK), fasting and postprandial concentrations of glucose, insulin and plasma lipids, post-heparin lipase activity, and apoE genotype. RESULTS: The expected positive associations between BMI, W and SSK and fasting and postprandial insulin were observed (r=0.42-0.65). Little association between glucose responses and any measures of adiposity was evident. Unexpectedly, there were no positive associations between measures of central adiposity (W and W/H) and fasting and postprandial TG responses, with a trend towards negative associations in this study group (TG AUC vs W, r=-0.23, P=0.097; TG IAUC vs W/H, r=-0.26, P=0.068). Subgroup analysis indicated that lack of a positive association between central adiposity and postprandial TG values was more evident in those with one E4 allele (r=-0.42, P=0.077) relative to non-E4 carriers (r=-0.16, P=0.430). The expected positive associations between insulin and TG responses were not observed (r=-0.03 to -0.36). CONCLUSION: In this ALP group the expected positive association between TG responses and a centralized distribution of body fat was not observed, particularly in individuals with an apoE4 genotype. Our findings are not in line with the view that there is a clear causal relationship between insulin resistance and the lipid abnormalities associated with ALP.

Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects

A predominance of small, dense low-density lipoprotein (LDL) is a major component of an atherogenic lipoprotein phenotype, and a common, but modifiable, source of increased risk for coronary heart disease in the free-living population. While much of the atherogenicity of small, dense LDL is known to arise from its structural properties, the extent to which an increase in the number of small, dense LDL particles (hyper-apoprotein B) contributes to this risk of coronary heart disease is currently unknown. This study reports a method for the recruitment of free-living individuals with an atherogenic lipoprotein phenotype for a fish-oil intervention trial, and critically evaluates the relationship between LDL particle number and the predominance of small, dense LDL. In this group, volunteers were selected through local general practices on the basis of a moderately raised plasma triacylglycerol (triglyceride) level (>1.5 mmol/l) and a low concentration of high-density-lipoprotein cholesterol (<1.1 mmol/l). The screening of LDL subclasses revealed a predominance of small, dense LDL (LDL subclass pattern B) in 62% of the cohort. As expected, subjects with LDL subclass pattern B were characterized by higher plasma triacylglycerol and lower high-density lipoprotein cholesterol (<1.1 mmol/l) levels and, less predictably, by lower LDL cholesterol and apoprotein B levels (P<0.05; LDL subclass A compared with subclass B). While hyper-apoprotein B was detected in only five subjects, the relative percentage of small, dense LDL-III in subjects with subclass B showed an inverse relationship with LDL apoprotein B (r=-0.57; P<0.001), identifying a subset of individuals with plasma triacylglycerol above 2.5 mmol/l and a low concentration of LDL almost exclusively in a small and dense form. These findings indicate that a predominance of small, dense LDL and hyper-apoprotein B do not always co-exist in free-living groups. Moreover, if coronary risk increases with increasing LDL particle number, these results imply that the risk arising from a predominance of small, dense LDL may actually be reduced in certain cases when plasma triacylglycerol exceeds 2.5 mmol/l.

Effects of oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment?

Objective: The objective of this study was to explore the relationship between low density lipoprotein (LDL) and dendritic cell (DC) activation, based upon the hypothesis that reactive oxygen species (ROS)-mediated modification of proteins that may be present in local DC microenvironments could be important as mediators of this activation. Although LDL are known to be oxidised in vivo, and taken up by macrophages during atherogenesis; their effect on DC has not been explored previously. Methods: Human DCs were prepared from peripheral blood monocytes using GM-CSF and IL-4. Plasma LDLs were isolated by sequential gradient centrifugation, oxidised in CuSO4, and oxidation arrested to yield mild, moderate and highly oxidised LDL forms. DCs exposed to these LDLs were investigated using combined phenotypic, functional (autologous T cell activation), morphological and viability assays. Results: Highly-oxidised LDL increased DC HLA-DR, CD40 and CD86 expression, corroborated by increased DC-induced T cell proliferation. Both native and oxidised LDL induced prominent DC clustering. However, high concentrations of highly-oxidised LDL inhibited DC function, due to increased DC apoptosis. Conclusions: This study supports the hypothesis that oxidised LDL are capable of triggering the transition from sentinel to messenger DC. Furthermore, the DC clustering–activation–apoptosis sequence in the presence of different LDL forms is consistent with a regulatory DC role in immunopathogenesis of atheroma. A sequence of initial accumulation of DC, increasing LDL oxidation, and DC-induced T cell activation, may explain why local breach of tolerance can occur. Above a threshold level, however, supervening DC apoptosis limits this, contributing instead to the central plaque core.

A stearic acid-rich diet improves thrombogenic and atherogenic risk factor profiles in healthy males

Objective: To determine whether healthy males who consumed increased amounts of dietary stearic acid compared with increased dietary palmitic acid exhibited any changes in their platelet aggregability, platelet fatty acid profiles, platelet morphology, or haemostatic factors.

Design: A randomized cross-over dietary intervention.

Subjects and interventions: Thirteen free-living healthy males consumed two experimental diets for 4 weeks with a 7 week washout between the two dietary periods. The diets consisted of ~30% of energy as fat (66% of which was the treatment fat) providing ~6.6% of energy as stearic acid (diet S) or ~7.8% of energy as palmitic acid (diet P). On days 0 and 28 of each dietary period, blood samples were collected and anthropometric and physiological measurements were recorded.

Results: Stearic acid was increased significantly in platelet phospholipids on diet S (by 22%), while on diet P palmitic acid levels in platelet phospholipids also increased significantly (8%). Mean platelet volume, coagulation factor FVII activity and plasma lipid concentrations were significantly decreased on diet S, while platelet aggregation was significantly increased on diet P.

Conclusion: Results from this study indicate that stearic acid (19 g/day) in the diet has beneficial effects on thrombogenic and atherogenic risk factors in males. The food industry might wish to consider the enrichment of foods with stearic acid in place of palmitic acid and trans fatty acids.

Atherogenic index of plasma and atherogenic coefficient are increased in major depression and bipolar disorder, especially when comorbid with tobacco use disorder

There is a robust comorbidity between mood disorders and cardiovascular disorder (CVD). The atherogenic index of plasma (AIP) and the atherogenic coefficient (AC) are important atherogenic indexes. The aims of this study were to delineate whether AIP and AC are increased in mood disorders especially when comorbid with tobacco use disorder (TUD).

Anti-Atherogenic Effects of a Phenol-Rich Fraction from Brazilian Red Wine (Vitis labrusca L.) in Hypercholesterolemic Low-Density Lipoprotein Receptor Knockout Mice

Moderate wine intake (i.e., 1-2 glasses of wine a day) is associated with a reduced risk of morbidity and mortality from cardiovascular disease. The aim of this study was to evaluate the anti-atherosclerotic effects of a nonalcoholic ethyl acetate fraction (EAF) from a South Brazilian red wine obtained from Vitis labrusca grapes. Experiments were carried out on low-density lipoprotein (LDL) receptor knockout (LDLr-/-) mice, which were subjected to a hypercholesterolemic diet and treated with doses of EAF (3, 10, and 30 mg/kg) for 12 weeks. At the end of the treatment, the level of plasma lipids, the vascular reactivity, and the atherosclerotic lesions were evaluated. Our results demonstrated that the treatment with EAF at 3 mg/kg significantly decreased total cholesterol, triglycerides, and LDL plus very low-density lipoprotein levels compared with control hypercholesterolemic mice. The treatment of mice with EAF at 3 mg/kg also preserved the vasodilatation induced by acetylcholine on isolated thoracic aorta from hypercholesterolemic LDLr-/- mice. This result is in agreement with the degree of lipid deposit on arteries. Taken together, the results show for the first time that the lowest concentration of an EAF obtained from a red wine produced in southern Brazil significantly reduced the progression of atherosclerosis in mice.

Anti-atherogenic and anti-angiogenic activities of polyphenols from propolis

Propolis is a polyphenol-rich resinous substance extensively used to improve health and prevent diseases. The effects of polyphenols from different sources of propolis on atherosclerotic lesions and inflammatory and angiogenic factors were investigated in LDL receptor gene (LDLr-/-) knockout mice. The animals received a cholesterol-enriched diet to induce the initial atherosclerotic lesions (IALs) or advanced atherosclerotic lesions (AALs). The IAL or AAL animals were divided into three groups, each receiving polyphenols from either the green, red or brown propolis (250 mg/kg per day) by gavage. After 4 weeks of polyphenol treatment, the animals were sacrificed and their blood was collected for lipid profile analysis. The atheromatous lesions at the aortic root were also analyzed for gene expression of inflammatory and angiogenic factors by quantitative real-time polymerase chain reaction and immunohistochemistry. All three polyphenol extracts improved the lipid profile and decreased the atherosclerotic lesion area in IAL animals. However, only polyphenols from the red propolis induced favorable changes in the lipid profiles and reduced the lesion areas in AAL mice. In IAL groups. VCAM, MCP-1, FGF, PDGF, VEGF, PECAM and MMP-9 gene expression was down-regulated, while the metalloproteinase inhibitor TIMP-1 gene was up-regulated by all polyphenol extracts. In contrast, for advanced lesions, only the polyphenols from red propolis induced the down-regulation of CD36 and the up-regulation of HO-1 and TIMP-1 when compared to polyphenols from the other two types of propolis. In conclusion, polyphenols from propolis, particularly red propolis, are able to reduce atherosclerotic lesions through mechanisms including the modulation of inflammatory and angiogenic factors. (C) 2012 Elsevier Inc. All rights reserved.

Brazilian nut consumption improves selenium status and glutathione peroxidase activity and reduces atherogenic risk in obese women

Studies have shown that there are inverse relationships between nut consumption and the reduction of cardiovascular risk. This study tested the hypothesis that daily consumption of Brazilian nuts would have a positive effect upon selenium (Se) status, erythrocyte glutathione peroxidase activity, lipid profile, and atherogenic risk in severely obese women. Thirty-seven severely obese women each consumed 1 Brazilian nut a day (290 mu g of Se a day) for 8 weeks. Blood Se concentrations, total erythrocyte glutathione peroxidase activity, lipid profile, and Castelli I and H indexes were evaluated before and after the nuts consumption. All the patients were Se deficient at baseline; this deficiency was remedied by the consumption of the Brazilian nut (P < .0001). The intake of Brazilian nuts promoted a significant increase in high-density lipoprotein cholesterol concentrations (P < .00001), which then resulted in a significant improvement of the Castelli I (P < .0002) and II (P < .0004) indexes. This study shows that obese people who implement daily consumption of Brazilian nuts can improve both Se status and lipid profile, especially high-density lipoprotein cholesterol levels, thereby reducing cardiovascular risks. (C) 2012 Published by Elsevier Inc.