Oxidized LDL Cholesterol Research Articles

Association Between Circulating Oxidized LDL Cholesterol Levels and Premature Myocardial Infarction: A Case-Control Study

Background: Acute myocardial infarction (MI) occurs less frequently in younger individuals compared to older ones. The development of atherosclerotic plaque is primarily linked to oxidized low-density lipoprotein cholesterol (Ox-LDL). Objectives: This study aimed to investigate circulating Ox-LDL levels in individuals with premature MI and compare them to controls without a history of ischemic heart disease. Methods: In this case-control study, 35 patients who experienced a premature MI within 24 hours of symptom onset and met the age criteria (men ≤ 55 years and women ≤ 65 years) were recruited as cases. For comparison, 35 age and sex-matched individuals without a history of ischemic heart disease were selected as controls. Results: Analysis of circulating Ox-LDL levels revealed a significant elevation in patients with premature MI compared to controls (2.25 ± 1.78 vs. 1.04 ± 1.17 µg/dL; P = 0.002). Elevated Ox-LDL levels were associated with a 1.70-fold increased risk of premature MI compared to healthy individuals (95% CI: 1.16 - 2.49; P = 0.007). Conclusions: This study demonstrates an association between elevated Ox-LDL levels and premature MI, particularly in younger individuals. Measuring Ox-LDL levels may help predict heart attack risk, and interventions aimed at reducing these levels could potentially prevent atherosclerosis.

OxLDL as a prognostic biomarker of plaque instability in patients qualified for carotid endarterectomy.

Atherosclerotic plaque instability increases the risk of stroke. As such, determining the nature of an instability atherosclerotic plaque may speed up qualification for carotid endarterectomy (CEA), thus reducing the risk of acute vascular events. The aim of the study was to determine the diagnostic value of oxidized LDL cholesterol (ox-LDL), matrix metalloproteinase 9 (MMP-9) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum as a prognostic markers of instability atherosclerotic plaques. Serum was collected from 67 patients who underwent CEA in accordance with the qualification criteria. The levels of ox-LDL, MMP-9 and 8-OHdG were assessed by ELISA. The predictive value of the markers was determined based on an ROC curve, and the cut-off points with the highest sensitivity and specificity were determined. Patients with unstable atherosclerotic plaque had significantly higher serum ox-LDL, MMP-9 and 8-OHdG values. It was found that in patients before CEA, ox-LDL >31.4 ng/mL was associated with an 82.5% probability of unstable atherosclerotic plaque, MMP-9 >113.1 ng/mL with 78.6%, and 8-OHdG >2.15 ng/mL with 64.7%. Multivariate regression analysis found ox-LDL to be an independent factor associated with plaque instability. Patients with unstable plaques tend to have higher serum levels of ox-LDL, MMP-9 and 8-OHdG compared to those with stable plaques. The optimal cut-off point for ox-LDL (AUC 0.86, p <0.0001) was 31.14 ng/mL, with 91.18% sensitivity and 78.79% specificity. The high sensitivity and specificity of ox-LDL suggests that it can be used as an independent marker of plaque instability.

A study on oxidized-LDL cholesterol in normolipidemic retinal vein occlusion

Background: Oxidized low-density lipoprotein (ox-LDL) has been implicated in atherosclerotic cardiovascular disease. Arteriolosclerosis is an important causative factor for retinal vein occlusion (RVO). Till, date there is dearth of literature on ox-LDL and RVO. Aims and Objectives: The objectives of this study were to see whether ox-LDL cholesterol is an independent risk factor in RVO with normal lipid profile. Materials and Methods: Lipid profiles and ox-LDL levels were assayed in 122 adult unilateral RVO cases and 142 age and sex matched controls in this 1 year old case–control study. Results: ox-LDL cholesterol levels were significantly elevated in RVO cases than controls (54.5±6.1 in cases vs. 36.6±5.6 in controls, P&lt;0.01), although serum lipid profiles were normal in both cases and controls. Conclusion: The ox-LDL-induced atherosclerosis may be responsible for the retinal venous occlusion in absence of other risk factors. Hence, screening for ox-LDL in RVO patients should be worth considering especially in patients with normal lipid profiles.

Oxidized LDL and Risk of Coronary Heart Disease

Oxidized LDL cholesterol (ox-LDL) is considered to be a key factor of initiating and accelerating coronary heart disease CHD and diabetes Mellitus DM , is associated with several mechanisms one of them Oxidative stress. The aim of this study was to find the association between ox- LDL ,HDL-C , TG , LDL-C and arylesterase , with CHD risk in different age groups in males and females , the difference in these risk factors can explain the sex difference and how much the changes in the risk factors levels in CHD and CHD with DM patients between age groups.&#x0D; Methods: determination biochemical parameters of serum blood of ox-LDL , TG , TC , HDL-c , LDL-c , S. Glucose and arylesterase activity were measured in cases male and females were carried CHD and CHD with DM .The cases divided in different the age groups (40-49) , (50-59) and (60-69) years and compered the result with control groups .&#x0D; Results: mean Value of ox-LDL and oxidation ratio of LDL show significantly higher at (p&lt;0.05) in CHD and (p&lt;0.001) in CHD with DM patient for females in the age group (40-49) years but in the males show the results significant decrease and different significant in others groups ,beside to effect Sex and age some the studied biochemistry parameters levels and signification decrease in HDL-C and arylesterase levels as antioxidant enzymes in females and male patient selected compared with control groups.

Age-associated reductions in cardiovagal baroreflex sensitivity are exaggerated in middle-aged and older men with low testosterone.

Aging is associated with reductions in cardiovagal baroreflex sensitivity (cBRS), which increases cardiovascular disease risk. Preclinical data indicate that low testosterone reduces cBRS. We determined whether low testosterone is associated with greater age-associated reductions in cBRS in healthy men. Twenty-six men categorized as young (N = 6; age = 31 ± 4 yr; testosterone = 535 ± 60 ng/dL), middle-aged/older with normal (N = 10; aged 56 ± 3 yr; testosterone = 493 ± 85 ng/dL) or low (N = 10; age = 57 ± 6 yr; testosterone = 262 ± 31 ng/dL) testosterone underwent recordings of beat-by-beat blood pressure and R-R interval during rest and two Valsalva maneuvers, and measures of carotid artery compliance. IL-6, C-reactive protein (CRP), oxidized LDL cholesterol, and total antioxidant status (TAS) were also measured in blood. Middle-aged/older men had lower cBRS compared with young men (17.0 ± 6.5 ms/mmHg; P = 0.028); middle-age/older men with low testosterone had lower cBRS (5.5 ± 3.2 ms/mmHg; P = 0.039) compared with age-matched men with normal testosterone (10.7 ± 4.0 ms/mmHg). No differences existed between groups during Phase II of the Valsalva maneuver; middle-aged/older men with low testosterone had reduced cBRS (4.7 ± 2.6 ms/mmHg) compared with both young (12.8 ± 2.8 ms/mmHg; P < 0.001) and middle-aged/older men with normal testosterone (8.6 ± 4.4 ms/mmHg; P = 0.046). There were no differences in oxidized LDL (P = 0.882) or TAS across groups (P = 0.633). IL-6 was significantly higher in middle-aged/older men with low testosterone compared with the other groups (P < 0.05 for all) and inversely correlated with cBRS (r = -0.594, P = 0.007). Middle-aged/older men had reduced carotid artery compliance compared with young, regardless of testosterone status (P < 0.001). These observations indicate that low testosterone in middle-aged/older men may contribute to reductions in cBRS. These data suggest that increased inflammation may contribute to reductions in cBRS.NEW & NOTEWORTHY Middle-aged/older men with low testosterone have accelerated reductions in cardiovagal BRS compared with middle-aged/older men with normal testosterone. Increased concentrations of the proinflammatory cytokine IL-6 appear to contribute to the reductions in cardiovagal BRS in men with low testosterone.

Childhood psychosocial stress is linked with impaired vascular endothelial function, lower SIRT1, and oxidative stress in young adulthood.

Adverse childhood experiences (ACEs) are psychosocial stressors that occur during sensitive developmental windows and are associated with increased lifetime cardiovascular disease (CVD) risk in a dose-dependent manner. Vascular endothelial dysfunction is a pathophysiological mechanism that promotes hypertension and CVD and may be a mechanism by which ACEs contribute to lifetime CVD risk. We examined whether exposure to ACEs is associated with reduced vascular endothelial function (VEF) in otherwise healthy, young adult women (20.7 ± 3 yr) with (ACE+) versus without (ACE-) ACEs, explored whether differences in circulating sirtuin 1 (SIRT1) or systemic oxidative stress could explain ACEs-related differences in VEF, and examined the ability of a pilot, 8-wk exercise intervention to augment VEF and SIRT1 or reduce oxidized LDL cholesterol (oxLDL) in ACE+ young adult women. Forty-two otherwise healthy young adults completed this study. Prior to the intervention, VEF (P = 0.002) and SIRT1 (P = 0.004) were lower in the ACE+ than ACE- group, but oxLDL concentrations were not different (P = 0.77). There were also significant relationships (P ≤ 0.04) among flow-mediated dilation (FMD), SIRT1, and oxLDL in the ACE+, but not ACE- group. Adjusting for circulating SIRT1 and oxLDL reduced the differences in FMD observed between groups (P = 0.10), but only SIRT1 was a significant adjuster of the means (P < 0.05). Finally, the exercise intervention employed was unable to enhance VEF or SIRT1 in the ACE+ exercise group. Our data suggest that ACEs likely increase susceptibility to hypertension and CVD by causing endothelial dysfunction, perhaps through a SIRT1 pathway-related mechanism.NEW & NOTEWORTHY Our study provides novel evidence that young adult women with moderate-to-severe adverse childhood experience (ACE) exposure present impaired endothelial function and lower circulating sirtuin 1 (SIRT1) concentrations than age-matched controls. However, an 8-wk exercise intervention was unable to augment endothelial function or SIRT1 concentrations in a subset of those with ACEs. Our data suggest that ACEs-related impairments in endothelial function may be secondary to decreased NO bioavailability via SIRT1 and/or oxidative stress-related mechanisms.

Kefir improves blood parameters and reduces cardiovascular risks in patients with metabolic syndrome

BackgroundMetabolic syndrome (MS) occurs when different metabolic and hemodynamic components change simultaneously, being one of the factors related to high mortality rates in patients with cardiovascular diseases. This study investigated the effects of the probiotic kefir on anthropometric and physiological parameters in human subjects with MS. Methodsforty-eight patients diagnosed with MS were assigned into two groups in this randomized, double-blind, placebo-controlled clinical trial. Kefir group (KG) and control group (CG) drank kefir beverage and curd (1.6 mL/kg for men or 1.9 mL/kg for women) for 12 weeks, respectively. Blood pressure, anthropometric, and biochemical parameters (fasting glycemia, glycated hemoglobin (HA1c), total cholesterol (TC), high density lipoprotein (HDLc), triglycerides (Tg), oxidized LDL cholesterol (oxLDL), high-sensitivity C-reactive protein (hs-CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinophosphokinase (CPK), γ-Glutamyl Transferase (γ-GT), urea nitrogen, urea, and creatinine were evaluated before and after treatment. The risk of cardiovascular events for the next ten years was calculated through the Framingham Score method. ResultsKefir intake decreased blood pressure, fasting glycemia, LDLc, non-HDLc, Tg, and oxLDL, and increased HDLc levels in women. Kefir also reduced the risk of cardiovascular events for the next ten years, although anthropometric parameters remained unchanged. ConclusionsKefir intake improved blood pressure, fasting glucose, and lipid levels, reducing oxLDL and the risk of developing cardiovascular events in the next ten years. These results suggest regular kefir intake may have positive effects on MS treatment.

The Association between Glycemic Control with Oxidant Status Parameters in Type 2 Diabetic Patients.

Purpose:Glycemic control is important in order to avoid LDLs increased susceptibility to oxidation in diabetic patients. This study assess the relationship between diabetes control with serum prooxidant-antioxidant balance (PAB), oxidized LDL cholesterol (oxLDLc), homocysteine and vitamin D levels in patients with type 2 diabetes.Material and methods:This was a cross-sectional study on three groups including 80 subjects as well (WGC) and poor (PGC) glycemic control and 40 healthy subjects. Presence of nephropathy and retinopathy were determined using IDF criteria. HbA1c level was determined with columnar chromatography using BioSystems kit. Serum PAB, homocysteine, oxLDLc and vitamin D levels were measured by the standard tests.Results:There was a significant association between PAB with PGC (P< 0.001), diabetic retinopathy (P< 0.01) and nephropathy (P< 0.01) in type 2 diabetic patients. Moreover, the results showed that vitamin D serum levels was significantly lower in PGC patients (P< 0.01), and diabetic patients with retinopathy (P< 0.01). Multiple linear regression analysis revealed that the vitamin D deficiency can predict the HbA1c variations by 77.7% (β=- 0.775) in subjects with type 2 diabetes mellitus (P<0.001).Conclusions:There was a significant association between prooxidant-antioxidant balance and vitamin D serum levels with diabetic complications. (www.actabiomedica.it)

Improvements in antioxidant status after agraz consumption was associated to reductions in cardiovascular risk factors in women with metabolic syndrome

ABSTRACT In this study were evaluated the effects of the chronic consumption of agraz (Vaccinium meridionale) on antioxidant status and oxidative stress markers in 40 women with metabolic syndrome (MetS) (47.2 ± 9.4 years) through a double-blind, crossover design study, in which participants consumed daily agraz or placebo during 4 weeks, separated by a 4-wk washout period. At the end of each intervention period, endogenous antioxidant enzymes activity, serum total antioxidant capacity (TAC) (ferric reducing ability of plasma [FRAP]; Oxygen Radical Absorbance Capacity [ORAC] and 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) [ABTS]), and oxidative stress markers (Oxo-2ʹ-deoxyguanosine (8-OHdG) and F2-isoprostane) were determined. Women who increased endogenous antioxidant enzymes activity and serum TAC after agraz consumption, compared to placebo, significantly reduced oxidative stress markers, total cholesterol, LDL-cholesterol (LDL-c) levels, and waist circumference, demonstrating beneficial effects in the group of women in whom antioxidant parameters increased after agraz consumption, evidencing an individual variability in response to the beverage consumed.

Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory?

BackgroundAn increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease.MethodsWe assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44–67] years and disease duration at study entry 5 [3–8] months; and 72% fulfilled the 1987 RA criteria at 2 years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5 years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C.ResultsAfter adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios.ConclusionsHigh-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.

Ameliorative effects of crocin on tartrazine dye-induced pancreatic adverse effects: a biochemical and histological study.

The present study aimed to analyze the impact of tartrazine (T) and crocin (Cr) applications on the pancreas tissues of the Wistar rats. A total of 40 Wistar rats were randomly divided into 4 groups with 10 rats in each group, including the Control, T, Cr, and T + Cr groups. After 3 weeks of application, the pancreatic tissues of the rats were removed under anesthesia and rat blood samples were obtained. Tissues were analyzed with biochemical and histopathological methods. It was determined that T administration increased malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), glucose, triglyceride, LDL, VLDL, and total cholesterol levels. However, it decreased reduced glutathione (GSH), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), and HDL levels when compared with the other groups. It was observed that Cr administration significantly increased GSH, SOD, CAT, TAS, and HDL levels when compared with the control group. In the T group, histopathological changes were observed in pancreatic tissue, leading to damages in exocrine pancreas and islets of Langerhans and increased caspase-3 immunoreactivity (p ≤ 0.001). Co-administration of Cr and T brought the biochemical and histopathological findings closer to the control group levels. The administration of T induced damage in the pancreas with the administered dose and frequency. Cr can increase the antioxidant capacity in pancreas tissue. Co-administration of T and Cr contributed to the reduction of the toxic effects induced by T. It could be suggested that Cr administration ameliorated T toxicity.

A Nutrient-Dense Supplement Shake Improves Weight Loss and Metabolic Markers in Overweight Individuals: A Multicenter, Randomized, Double Blind, Placebo-Controlled Trial

Abstract Objectives To determine if greater weight loss and improvement in metabolic outcomes could be achieved with twice daily consumption of a proprietary supplement shake containing high protein and fiber (HPF) as compared to an isocaloric low protein, lower fiber placebo (P). Methods In an independently conducted randomized, double-blind, placebo-controlled, multi-center clinical trial, healthy overweight and obese adults (n = 206, BMI 27–35 kg/m2, 70% Female) were equally assigned to HPF or P. All participants were instructed to follow a 500-calorie deficit diet from estimated daily energy requirements using a dietary exchange program and were asked to consume HPF or P 30 min before breakfast and lunch for 12 weeks. The supplement was a commercially available product composed of protein, fruit, vegetable, and plant powders, as well as vitamins, minerals, pre-, and probiotics. Body weight, body composition, and blood samples were collected at days (D) 0 and 84. Statistics were conducted by ANCOVA or repeated measure ANCOVA modeling using sex and baseline values as covariates, with time and treatment as within- and between-subject variables, respectively. Per protocol analyses were included for the 133 adults who completed the study. Results Weight loss occurred throughout the study in both groups. HPF had greater weight loss at D 84 vs P (–4.0% vs −2.2% body weight, respectively; P &amp;lt; 0.05). Total cholesterol, LDL, and oxidized LDL decreased to a greater extent following HPF at D 84 (P &amp;lt; 0.05 vs D 0 and vs P), with no change in HDL cholesterol. The increase in serum adiponectin from D 0 to D 84 was greater in HPF vs P (P &amp;lt; 0.05) with no change in leptin. Percent body fat tended to decrease throughout the study in both groups (HPF: −1.44%, P: −1.27%; P = 0.056) with no differences between groups. There were no clinically relevant changes in assessed safety outcomes in either group. Conclusions A HPF supplement taken as a preload before breakfast and lunch improved weight loss and metabolic outcomes such as total, LDL and oxidized LDL cholesterol compared to a calorie-matched placebo. This study suggests nutrient factors other than calorie reduction alone influence the success of a weight loss regimen, potentially including nutrient density, protein and fiber content. This trial was registered at clinicaltrials.gov as NCT03057873. Funding Sources This study was funded by Beachbody, LLC.

The effect of green coffee extract supplementation on serum oxidized LDL cholesterol and total antioxidant capacity in patients with dyslipidemia: A randomized, double-blind, placebo-controlled trial

IntroductionPrevious studies on laboratory animals have evaluated the effects of CGA (chlorogenic acids) rather than GCBE (green coffee bean extract), and few studies have been conducted on human models. Thus, the purpose of the present study was to assess the effect of GCBE consumption on serum oxidized LDL-cholesterol (OX-LDL) and total antioxidant capacity (TAC) on patients with dyslipidemia. MethodIn this randomized, placebo-controlled, clinical trial, 70 male participants (age range 30–55 years) were assigned from the outpatient clinic of Arvand Petrochemical Company in Mah-shahr, Ahwaz, Iran to use 800 mg/day GCBE supplements or placebo for 8 weeks. Serum TAC and OX-LDL were determined by enzyme-linked immunosorbent assay. ResultsCompared with the placebo, GCBE intake led to a significant reduction in OX-LDL (−31.18 ng/ml) (P-value = <0.001) and a significant increase in TAC (71.73 μmol/l) concentration (P-value = 0.029). In the intervention group, GCBE supplementation resulted in a significant reduction in Oxidized LDL of −16.08 ± 33.30 (ng/ml) (P-value = 0.006), compared to baseline. ConclusionsThe current trial showed that the intake of 800 mg per day of GCBE may have favorable effects on TAC, and OX-LDL in patients with dyslipidemia. However, further studies are required to confirm the veracity of these results.

The Effect of Aerobic Exercise Training on Ox-LDL Levels and Some Cardiovascular Risk Factors in Women with Obesity

BackgroundToday, the prevalence of obesity is seen as a major social challenge, affecting the general health of societies, which creates irreversible psychological, social, and economic consequences. In this regard, exercise training is one of the most important interventions in preventing and controlling obesity and the associated metabolic factors, which can be an appropriate and low-cost option for promoting community health and to some extent, managing metabolic diseases.ObjectivesThe present study was aimed at evaluating the impact of eight weeks of aerobic exercises on the levels of oxidized LDL cholesterol (Ox-LDL) and cardiovascular risk factors among obese and overweight females.MethodsThis study was conducted in Gachsaran, Iran in 2018. Following a public call for inclusion as part of this quasi-experimental study, 22 obese women who met the inclusion criteria that was set for the study were chosen and were then divided into experimental (exercise training) (n = 11) and control (n = 11) groups. The subjects in the experimental group ran for eight weeks, three sessions per week for 45 minutes at an intensity of 55% to 65% of maximal oxygen consumption (Vo2max). Independent and paired sample t-test were used to account for the variations. For statistical analysis SPSS-21 software was used, and the significance level was set to be less than P < 0.05.ResultsThe findings indicated that the participants’ body mass indices in the experimental group significantly decreased (P < 0.001). In addition, it was found that insulin resistance (HOMA-IR), insulin, glucose and lipoproteins (LDL-TC-TG), and C-reactive protein (CRP) were significantly diminished (P < 0.001), whereas the high-density lipoprotein (HDL) level went up (P < 0.001) following the treatment. No significant changes in Ox-LDL were found after eight weeks of aerobic exercise training (P = 0.07).ConclusionsIt seems that eight weeks of exercise training with decreasing anthropometric indices, CRP levels, and insulin resistance, even without changing the levels of Ox-LDL, can prevent obesity and metabolic complications.

Unhealthy lifestyle and oxidative damage in childhood obesity.

Oxidized LDL cholesterol (oxLDL) has been considered as a sensor of oxidative stress (OS) in childhood obesity. We integrated and related our oxLDL existing results previously assessed in overweight/obese children to lifestyle variables to investigate OS-related lifestyle variables. 178 Caucasian children/adolescents have been evaluated and according to BMI percentiles have been classified as normal weight (BMI < 75th); overweight (BMI 75-97th) and obese (BMI > 97th). Serum oxLDL levels have been measured. The dietary habits and physical activity have been also assessed. No differences between normal weight and overweight/obese children were detected according to the total score of dietary habits section. Normal weight subjects reported a higher total physical activity score (p = 0.001) compared to overweight/ obese children. No correlation between oxLDL and total dietary habits and physical activity scores was noted. Increased oxLDL in subjects drinking < 1L/day of water (p = 0.022) and in daily consumers of chocolate drinks at breakfast (p = 0.029) was observed, while a decreased oxLDL was reported in subjects consuming a breakfast based mainly on fruits (p = 0.004). Moreover, "high-fat diet" and "always eating a dessert at the end of the meal" were correlated with increased oxLDL with a trend towards significance. As regards physical activity, no correlations were observed. Diet and physical activity may not have an immediate impact on OS response in children with or without obesity. Unhealthy lifestyle, including increased fat, simple sugar intake, poor water intake, emerged as external exposome predictors of OS, that may be monitored to improve health status. Level III,case-control analytic studies.

Measuring the impact of olive pomace enriched biscuits on the gut microbiota and its metabolic activity in mildly hypercholesterolaemic subjects

PurposeOlive pomace is a major waste product of olive oil production but remains rich in polyphenols and fibres. We measured the potential of an olive pomace-enriched biscuit formulation delivering 17.1 ± 4.01 mg/100 g of hydroxytyrosol and its derivatives, to modulate the composition and metabolic activity of the human gut microbiota.MethodsIn a double-blind, controlled parallel dietary intervention 62 otherwise healthy hypercholesterolemic (total plasma cholesterol 180–240 mg/dl) subjects were randomly assigned to eat 90 g of olive pomace-enriched biscuit (olive-enriched product, OEP) or an isoenergetic control (CTRL) for 8 weeks. Fasted blood samples, 24-h urine and faecal samples were collected before and after dietary intervention for measurement of microbiota, metabolites and clinical parameters.ResultsConsumption of OEP biscuits did not impact on the diversity of the faecal microbiota and there was no statistically significant effect on CVD markers. A trend towards reduced oxidized LDL cholesterol following OEP ingestion was observed. At the genus level lactobacilli and Ruminococcus were reduced in OEP compared to CTRL biscuits. A trend towards increased bifidobacteria abundance was observed after OEP ingestion in 16S rRNA profiles, by fluorescent in situ hybridization and by qPCR. Targeted LC–MS revealed significant increases phenolic acid concentrations in 24-h urine following OEP ingestion and 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid, derivatives of hydroxytyrosol, were elevated in blood. A sex effect was apparent in urine small phenolic acid concentrations, and this sex effect was mirrored by statistically significant differences in relative abundances of faecal bacteria between men and women.ConclusionIngestion of OEP biscuits led to a significant increase in the metabolic output of the gut microbiota with an apparent sex effect possibly linked to differences in microbiota makeup. Increased levels of homovanillic acid and DOPAC, thought to be involved in reducing oxidative LDL cholesterol, were observed upon OEP ingestion. However, OEP did not induce statistically significant changes in either ox-LDL or urinary isoprostane in this study.

Deletion of JNK2 prevents vitamin-D-deficiency-induced hypertension and atherosclerosis in mice

The c-Jun N-terminal kinase 2 (JNK2) signaling pathway contributes to inflammation and plays a key role in the development of obesity-induced insulin resistance and cardiovascular disease. Macrophages are key cells implicated in these metabolic abnormalities. Active vitamin D downregulates macrophage JNK activation, suppressing oxidized LDL cholesterol uptake and foam cell formation and promoting an anti-inflammatory phenotype. To determine whether deletion of JNK2 prevents high blood pressure and atherosclerosis known to be induced by vitamin D deficiency in mice, we generated mice with knockout of JNK2 in a background susceptible to diet-induced atherosclerosis (LDLR−/−). JNK2−/− LDLR−/− and LDLR−/− control mice were fed vitamin D-deficient chow for 8 weeks followed by vitamin D-deficient high fat diet (HFD) for 10 weeks and assessed before and after HFD. There was no difference in fasting glucose, cholesterol, triglycerides, or free fatty acid levels. However, JNK2−/− mice, despite vitamin D-deficient diet, had 20–30mmHg lower systolic (SBP) and diastolic (DBP) blood pressure before HFD compared to control mice fed vitamin D-deficient diets, with persistent SBP differences after HFD. Moreover, deletion of JNK2 reduced HFD-induced atherosclerosis by 30% in the proximal aorta when compared to control mice fed vitamin D-deficient diets. We have previously shown that peritoneal macrophages obtained from LDLR−/− mice fed vitamin D-deficient HFD diets have higher foam cell formation compared to those from mice on vitamin D-sufficient HFD. The increased total cellular cholesterol and modified cholesterol uptake in macrophages from mice on vitamin D-deficient HFD were blunted by deletion of JNK2. These data suggest that JNK2 signaling activation is necessary for the atherosclerosis and hypertension induced by vitamin D deficiency.

Abstract 19716: Zebrafish Larvae as a Model System For High-throughput Screens of Early-stage Atherosclerosis

Introduction: A high-cholesterol diet has been reported to induce vascular deposition of lipids and oxidized LDL cholesterol in macrophages and other cell types in 15 day-old zebrafish larvae. However, results were based on small samples, and little is known about the heterogeneity of effect within and between conditions, the image quantification procedure used, and the influence of dietary energy. We intend to perform large-scale genetic and compound screens for coronary heart disease, and aimed to confirm or refute if zebrafish larvae are a suitable model system. Methods: In total, 940 transgenic zebrafish larvae were fed on one of six diets between 5 and 10 days post-fertilization (dpf), to examine main effects of, and interactions between dietary energy and cholesterol. At 10 dpf, we assessed body length and acquired optical sections of the dorsal aorta and caudal vein using an automated positioning system, fluorescence microscope and CCD camera. Atherogenic traits were quantified using a custom-written image analysis pipeline in Ilastik, CellProfiler and ImageJ, and larvae were used to assess whole body levels of total cholesterol, triglycerides and glucose using enzymatic assays. Associations were adjusted for body length, ether - used to prepare the high-cholesterol diet - and batch. Results: A high-energy diet resulted in elevated triglyceride levels (p=7.8E-3) - especially in the presence of high dietary cholesterol (p-interaction=0.01) - and in more vascular infiltration by lipids (p=1.0E-12), and co-localising lipids and macrophages (p=0.04), independently of dietary cholesterol. A high-cholesterol diet resulted in higher glucose levels (p=2.1E-3), and in more vascular infiltration by lipids (p=0.01), and co-localising lipids and neutrophils (p=0.04), and lipids, neutrophils and macrophages (p=0.01), independently of dietary energy. Qualitative analyses showed that vascular lipid deposits typically contain oxidised LDL cholesterol, and are located at bifurcation sites of the endothelium. Conclusions: Zebrafish larvae represent a promising model system for high-throughput, image-based screens of early-stage atherosclerosis, and dietary energy and cholesterol induce distinct atherogenic traits as early as 10 dpf.

Coenzyme Q10 and oxidative stress, the association with peripheral sensory neuropathy and cardiovascular disease in type 2 diabetes mellitus

ObjectiveOur study aimed to explore associations between metabolic control, oxidative stress and coenzyme Q10 (CoQ10) in relation to diabetes complications in a representative population of type 2 diabetes. Research design and methodsA geographic cohort of 156 subjects was recruited. Serum concentrations of CoQ10 and vitamin E were measured by HPLC. ROS was determined by free oxygen radicals testing (FORT). Glutaredoxin (Grx) activity, oxidized LDL cholesterol (oxLDLc), high sensitive CRP (hsCRP), HbA1c, urine albumin, serum creatinine, serum cystatin C, and plasma lipids were assayed with routine laboratory protocols. ResultsSerum CoQ10 was higher than in nondiabetics. HbA1c, fP-glucose, hyperlipidemia, inflammation (hsCRP), and increased BMI were associated with signs of oxidative stress as increased levels of FORT, Grx activity and/or increased levels of oxLDLc Oxidative stress was found to be strongly correlated with prevalence of cardiovascular disease (CVD) and peripheral sensory neuropathy (PSN). In both gender groups there were positive correlations between CoQ10 and oxLDLc, and between BMI and the ratio CoQ10/chol. Grx activity was inversely correlated to oxLDLc and CoQ10. Women with CVD and PSN had higher waist index, oxLDLc, and FORT levels compared to men but lower CoQ10 levels. Men had worse kidney function and lower vitamin E. Multiple regression analysis showed increased levels of CoQ10 to be significantly correlated with increased levels of cholesterol, triglycerides, vitamin E, fB-glucose and BMI. ConclusionsHyperlipidemia, hyperglycemia and inflammation were associated with oxidative stress, which was correlated to the prevalence of diabetes complications. CoQ10 was increased in response to oxidative stress. There were gender differences in the risk factors associated with diabetes complications.

Clinical evaluation of formula F105, designed and developed to address elevated oxidized LDL Cholesterol (oxLDL) levels

Clinical evaluation of formula F105, designed and developed to address elevated oxidized LDL Cholesterol (oxLDL) levels