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Background: Dietary flavonoid intake is associated with a reduced risk of some cardiometabolic disorders, attributed in part to their claimed anti-inflammatory activity. Our aim was to investigate the potential association between specific urine flavonoid metabolites, liver enzymes, and inflammatory status in individuals with metabolic syndrome (MetS). Methods: In this cross-sectional study, clinical and dietary data from 267 participants, aged 55 to 75 years, participating in the PREDIMED Plus study (PREvención con DIeta MEDiterránea) were analyzed. At the baseline, spot urine samples were collected and seven urinary flavonoid metabolites were quantified using ultra-performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS). Liver enzymes, inflammatory scores, and urinary flavonoid concentrations were inverse normally transformed. Results: Adjusted linear regression models showed an inverse association between urinary citrus flavanone concentrations and gamma-glutamyl transferase (GGT) (all p-values

Background Cell membrane fatty acid composition has been related to inflammation and cardiovascular risk. Dysregulation of HDL functionis also considered a cardiovascular risk factor. Objective We aimed to investigate whether the content of cell membrane fatty acids and HDL functionality are linked to each other as well as to inflammation. Methods This cross-sectional analysis involved 259 participants (67.9 y) with overweight/obesity (body mass index 29.5 kg/m2) from a coronary heart disease case-control study nested within the PREDIMED trial for which HDL functional parameters (Apolipoproteins (Apo) A-1, A-IV and C-III, cholesterol efflux capacity (CEC), HDL oxidative inflammatory index (HOII), sphingosine-1-phosphate (S1P), serum amyloid A (SAA) and complement-3 (C3) protein) were quantified. We also assessed 22 fatty acids in blood cell membranes using gas chromatography and inflammatory markers (interferon-γ (IFNγ) and interleukins (IL)-1b, IL-6, IL-8, and IL-10) in serum. Associations of HDL-related variables with cell membrane fatty acids and with inflammatory markers were assessed using multivariable linear regression analyses with elastic net penalty. Results ApoA-1, ApoC-III, CEC, HOII, S1P, and SAA, but not ApoA-IV and C3 protein, were associated with membrane fatty acids. S1P and SAA were directly associated with IL-6, while ApoA-1 and C3 protein showed inverse association with IL-6. Specific fatty acids including 14:0 and long chain n-6 fatty acids being negatively and positively, respectively, associated with IL-8 were also found to be positively associated with SAA. Conclusion This study suggests interrelationships between indicators of inflammation and both blood cell membrane fatty acid composition and HDL structure/functional parameters in a Mediterranean population at high cardiovascular disease risk.

Our aim was to assess the combination of olive tree-related extracts with the most favorable profile of in vitro bioactive properties. We tested the antioxidant (increment of low-density lipoprotein resistance against oxidation), vasoactive (promotion of nitric oxide release and decrease of endothelin-1 production in human umbilical vein endothelial cells), anti-inflammatory (decrease of the endothelial production of vascular cell adhesion molecule-1), and antithrombotic (reduction of the endothelial release of plasminogen activator inhibitor-1) capacities of six phenolic extracts and three triterpenic acid solutions (Ps and Ts, respectively). We tested extracts alone and in combination, at nutritional (Ps: 0.05–0.5 mol/L; Ts: 0.001–0.1 mol/L) and nutraceutical doses (Ps: 1–10 mol/L; Ts: 0.25–10 mol/L). The combination of Ps rich in 3,4-dihydroxyphenylglycol (76%, P2), hydroxytyrosol (95%, P3), and oleuropein (70%, P4) (final nutritional concentration: 0.15 mol/L; final nutraceutical concentration: 3 mol/L) was the best in order to prepare functional products and nutraceuticals with cardioprotective properties, despite the fact that the isolated extract with the greatest in vitro properties was P5 (75% oleocanthal), suggesting a potential synergistic effect among different olive components., Spanish Ministry of Economy, Industry and Competitiveness, through the FEDER INNTERCONECTA Program of the Center for Industrial Technological Development (CDTI), Junta de Andalucía ITC-20151142 EXP 00083147, Instituto de Salud Carlos III European Commission CB06/03/0028 CD17/00122 CES12/025 JR17/00022, European Commission

We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini&ndash, Hochberg-adjusted p-value were &gt, 1.30 and their absolute z-scores were &gt, 2.0 (&ge, 2.0 meant &ldquo, upregulation&rdquo, and &le, &minus, 2.0 &ldquo, downregulation&rdquo, ). Cancer signaling pathways were the most upregulated ones in T2D (z-score = 2.63, &minus, log(p-value) = 32.3, 88.5% (n = 906) of the total differentially expressed genes located in these pathways). In particular, integrin (z-score = 2.52, &minus, log(p-value) = 2.03) and paxillin (z-score = 2.33, &minus, log(p-value) = 1.46) signaling pathways were predicted to be upregulated, whereas the Rho guanosine diphosphate (Rho-GDP) dissociation inhibitor signaling pathway was predicted to be downregulated in T2D individuals (z-score = &minus, 2.14, &minus, log(p-value) = 2.41). Our results suggest that, at transcriptional expression level, elderly individuals with T2D present an increased activation of signaling pathways related to neoplastic processes, T-cell activation and migration, and inflammation.

The consumption of antioxidant-rich foods such as virgin olive oil (VOO) promotes high-density lipoprotein (HDL) anti-atherogenic capacities. Intake of functional VOOs (enriched with olive/thyme phenolic compounds (PCs)) also improves HDL functions, but the gene expression changes behind these benefits are not fully understood. Our aim was to determine whether these functional VOOs could enhance the expression of cholesterol efflux-related genes. In a randomized, double-blind, crossover, controlled trial, 22 hypercholesterolemic subjects ingested for three weeks 25 mL/day of: (1) a functional VOO enriched with olive oil PCs (500 mg/kg), (2) a functional VOO enriched with olive oil (250 mg/kg) and thyme PCs (250 mg/kg, FVOOT), and, (3) a natural VOO (olive oil PCs: 80 mg/kg, control intervention). We assessed whether these interventions improved the expression of cholesterol efflux-related genes in peripheral blood mononuclear cells by quantitative reverse-transcription polymerase chain reactions. The FVOOT intervention upregulated the expression of CYP27A1 (P = 0.041 and P = 0.053, versus baseline and the control intervention, respectively), CAV1 (P = 0.070, versus the control intervention), and LXR&beta, RXR&alpha, and PPAR&beta, /&delta, (P = 0.005, P = 0.005, and P = 0.038, respectively, relative to the baseline). The consumption of a functional VOO enriched with olive oil and thyme PCs enhanced the expression of key cholesterol efflux regulators, such as CYP27A1 and nuclear receptor-related genes.

AIM To determine whether circulating antibodies against oxidized low-density lipoprotein (LDL; OLAB) levels are associated with acute myocardial infarction (AMI) in individuals without classical cardiovascular risk factors. METHODS A case-control study including 34 first AMI patients without classical risk factors (smoking, dyslipidemia, hypertension or diabetes) and 45 population-based healthy controls. RESULTS There were no differences in anthropometric variables between cases and controls. Oxidized LDL levels were similar in both groups. Total cholesterol, LDL cholesterol, apolipoprotein B and physical activity were lower in cases than in controls. OLAB levels were also lower in cases than controls (128 versus 447 U/l, P < 0.001). After adjusting for age, oxidized LDL and physical activity, participants with OLAB levels of 165 U/l or less had a higher risk of AMI (odds ratio, OR = 7.48, 95% confidence interval: 1.57-35.66). When the model was fitted with OLAB as a continuous variable, the natural logarithm (LnOLAB) levels were independently associated with AMI with an OR of 0.40 (95% confidence interval: 0.19-0.86). After adjusting the model by Framingham-risk-adapted score and oxidized LDL, the LnOLAB levels maintained their independent association (OR of 0.43, 95% confidence interval: 0.23-0.79). CONCLUSION First AMI patients without classical risk factors had lower levels of OLAB compared with healthy controls. It is likely that the immunological reaction due to oxidized LDL participates as a preventive factor in the physiopathology of atherosclerosis.

To investigate whether the ingestion of olive oil having different phenolic contents influences the expression of blood pressure-related genes, involved in the renin–angiotensin–aldosterone system, in healthy humans. A randomized, double-blind, crossover human trial with 18 healthy subjects, who ingested 25 mL/day of olive oils (1) high (366 mg/kg, HPC) and (2) low (2.7 mg/kg, LPC) in phenolic compounds for 3 weeks, preceded by 2-week washout periods. Determination of selected blood pressure-related gene expression in peripheral blood mononuclear cells (PBMNC) by qPCR, blood pressure and systemic biomarkers. HPC decreased systolic blood pressure compared to pre-intervention values and to LPC, and maintained diastolic blood pressure values compared to LPC. HPC decreased ACE and NR1H2 gene expressions compared with pre-intervention values, and IL8RA gene expression compared with LPC. The introduction to the diet of an extra-virgin olive oil rich in phenolic compounds modulates the expression of some of the genes related to the renin–angiotensin–aldosterone system. These changes could underlie the decrease in systolic blood pressure observed.