Plasma Oxidized Low-density Lipoprotein Research Articles

Instant and short-term effects of acupuncture for depression and anxiety in unstable angina pectoris patients with percutaneous coronary interventions.

Patients with unstable angina pectoris (UAP) usually present anxiety or depression during percutaneous coronary intervention (PCI). This study sought to investigate the instant and short-term effects of acupuncture for anxiety and depression in UAP patients with PCI. A total of 210 UAP patients who underwent PCI were recruited and randomly assigned (1:1:1) to acupuncture, placebo, or control groups. Enzyme-linked immunosorbent assay was used to detect the levels of fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), high-sensitivity C-reactive protein (Hs-CRP), advanced oxidation protein products (AoPPs), and oxidized low-density lipoprotein (OX-LDL). Serial questionnaires with the Hamilton Anxiety (HAMA) scale and the Pittsburgh Sleep Quality Index were evaluated, and heart rate variability indicators were obtained. Primary end-point: low frequency/high frequency (HF) was lower in the electroacupuncture group (p = 0.014), while standard deviation of normal-to-normal intervals, average standard deviation of normal-to-normal intervals, percentage of successive intervals that differ more than 50 ms, and HF were increased with acupuncture (p = 0.018, p = 0.043, p = 0.016, and p = 0.002, respectively). Secondary end-point: significant improvements in anxiety levels (HAMA) were observed in the three groups (p < 0.001). The fasting insulin and HOMA-IR levels were similar between the control group and the acupuncture group (p = 0.285 and p = 0.165, respectively). The levels of IL-6 and AoPPs differed among the three groups (p = 0.021 and p < 0.001, respectively). However, no significant differences were found in fasting plasma glucose, fasting c-peptide, Hs-CRP, and OX-LDL levels among the three groups (p = 0.585, p = 0.611, p = 0.902, and p = 0.756, respectively). In this study, short-term acupuncture may potentially relieve clinical symptoms before PCI treatment. ClinicalTrials.gov, identifier (NCT03789344).

Efficacy of Hydroxytyrosol-Rich Food Supplements on Reducing Lipid Oxidation in Humans.

In the present study we report the efficacy of two food supplements derived from olives in reducing lipid oxidation. To this end, 12 healthy volunteers received a single dose (25 mL) of olive phenolics, mainly hydroxytyrosol (HT), provided as a liquid dietary supplement (30.6 or 61.5 mg HT), followed by an investigation of two reliable markers of oxidative stress. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 h post-intake. Plasma-oxidized low-density lipoprotein (oxLDL) cholesterol levels were measured with ELISA using a monoclonal antibody, while F2-isoprostanes (F2-IsoPs) were quantified in urine with UHPLC-DAD-MS/MS. Despite the great variability observed between individuals, a tendency to reduce lipoxidation reactions was observed in the blood in response to a single intake of the food supplements. In addition, the subgroup of individuals with the highest baseline oxLDL level showed a significant (p < 0.05) decrease in F2-IsoPs at 0.5 and 12 h post-intervention. These promising results suggest that HT supplementation could be a useful aid in preventing lipoxidation. Additionally, people with a redox imbalance could benefit even more from supplementing with bioavailable HT.

Objectively Measured Vigorous‐Intensity Physical Activity is Related to Endothelial Function in Midlife and Older Men but not in Estrogen‐Deficient Postmenopausal Women

BackgroundAerobic exercise training is consistently associated with enhanced vascular endothelial function via suppression of oxidative stress in midlife/older (ML/O; 50 years) men but not in estrogen‐deficient postmenopausal women (E‐PMW). It is unclear if chronic physical activity (PA) patterns assessed under free‐living conditions, including sedentary behavior and vigorous exercise, are related to endothelial function among ML/O men or E‐PMW. We investigated if objectively measured PA patterns were associated with endothelial function in ML/O adults and the potential mechanisms involved.Methods172 ML/O adults were included for analysis (67 ± 7 years; 85M/87W). Endothelium‐dependent dilation was assessed via brachial artery flow‐mediated dilation (FMDBA), a bioassay of endothelial function. PA was assessed over 3‐7 days via wrist‐worn accelerometers (GENEactiv), which measured sedentary time and light, moderate, and vigorous activity. The relations between endothelial function and PA were examined using simple and stepwise linear regression. Multiple linear regression was used to examine the correlation between endothelial function and PA when controlling for conventional cardiovascular disease risk factors. Plasma oxidized low‐density lipoprotein (OxLDL) concentrations and total antioxidant status were used as markers of oxidative stress and antioxidant defenses, respectively. Interleukin‐6, tumor necrosis factor‐α, and C‐reactive protein concentrations were examined to assess chronic low‐grade inflammation. Mediation analysis was used to determine the potential for changes in oxidative stress, antioxidant defenses, and inflammation as mechanisms mediating the relation between PA and endothelial function.ResultsIn the entire cohort of subjects, FMDBA was negatively associated with sedentary time (R2=0.04; p=0.01), not associated with light PA (R2=0.02; p=0.09), and positively associated with moderate (R2=0.03; p=0.04) and vigorous (R2=0.06; p&lt;0.01) PA. Only sedentary time (R2=0.06; p=0.02) and vigorous PA (R2=0.11; p&lt;0.01) were associated with FMDBA in ML/O men. No PA parameters were associated with FMDBA in E‐PMW (all p&gt;0.05). Stepwise linear regression revealed vigorous PA primarily mediated the effects of PA on FMDBA in ML/O men (R2=0.10; p&lt;0.01). When controlling for age, blood pressure, body mass index, triglycerides, high‐density lipoprotein, low‐density lipoprotein, and fasting glucose, vigorous PA independently predicted FMDBA in ML/O men (R2=0.05; p=0.05) but not in E‐PMW (R2=0.03; p=0.18). Plasma OxLDL concentrations mediated 13.5% of the group effect of vigorous PA on FMDBA (p&lt;0.01); no other plasma markers had a mediating effect (all p&gt;0.05).ConclusionsObjectively measured PA, primarily vigorous PA, is positively associated with endothelial function in ML/O men but not in E‐PMW. This relation is mediated, in part, by oxidative stress. These associations are consistent with findings that aerobic exercise training does not improve endothelial function in E‐PMW. Alternative strategies to improve endothelial function in E‐PMW are needed.

Choline Supplementation Does Not Promote Atherosclerosis in CETP-Expressing Male Apolipoprotein E Knockout Mice

Dietary trimethylamines, such as choline, metabolized by intestinal microbiota to trimethylamine are absorbed by the gut and oxidized to trimethylamine N-oxide (TMAO). The objective of this study was to determine the effect of choline supplementation on atherosclerosis progression in Apoe−/− mice expressing human cholesterol ester transfer protein (hCETP) using the same diets as in previously reported studies. Mice expressing hCETP, after transfection with AAV2/8-hCETP, were fed an 18% protein diet with either 0.09% (standard chow), 0.5% or 1% choline for 16 weeks. Control mice not transfected with hCETP were fed 1% choline. Dietary choline supplementation increased plasma TMAO levels at 8 and 16 weeks. When atherosclerotic lesions were measured in the thoracic aorta and aortic root, there were no differences between any of the treatment groups in the amount of plaque development at either site. Throughout the study, no significant changes in plasma lipids or major classes of lipoproteins were observed in hCETP-expressing mice. Plasma-oxidized low density lipoprotein, myeloperoxidase and high density lipoprotein inflammatory index were measured at 16 weeks, with no significant changes in any of these inflammatory markers between the four treatment groups. Despite increasing plasma TMAO levels, dietary choline supplementation in Apoe−/− mice expressing hCETP did not promote atherosclerosis.

In Vitro Studies Toward the Use of Chitin as Nutraceutical: Impact on the Intestinal Epithelium, Macrophages, and Microbiota.

ScopeChitin, the most abundant polysaccharide found in nature after cellulose, is known for its ability to support wound healing and to lower plasma‐oxidized low‐density lipoprotein (LDL) levels. Studies have also revealed immunomodulatory potential but contradicting results are often impossible to coalesce through usage of chitin of different or unknown physicochemical consistency. In addition, only a limited set of cellular models have been used to test the bioactivity of chitin.Methods and ResultsChitin is investigated with well‐defined physicochemical consistency for its immunomodulatory potency using THP‐1 macrophages, impact on intestinal epithelial barrier using Caco‐2 cells, and fermentation by fecal‐derived microbiota. Results show that chitin with a degree of acetylation (DA) of ≈83%, regardless of size, does not affect the intestinal epithelial barrier integrity. Large‐sized chitin significantly increases acetic acid production by gut microbiota without altering the composition. Exposure of small‐sized chitin to THP‐1 macrophages lead to significantly increased secretion of IL‐1β, IL‐8, IL‐10, and CXCL10 in a multi‐receptor and clathrin‐mediated endocytosis dependent manner.ConclusionsThese findings indicate that small‐sized chitin does not harm the intestinal barrier nor affects SCFA secretion and microbiota composition, but does impact immune activity which could be beneficial to subjects in need of immune support or activation.

Intake of Alpha-Linolenic Acid-Rich Perilla frutescens Leaf Powder Decreases Home Blood Pressure and Serum Oxidized Low-Density Lipoprotein in Japanese Adults.

Oxidized low-density lipoprotein (Ox-LDL) is known to be highly atherogenic. Thus, decreasing the blood levels of Ox-LDL through dietary means is an important approach to reduce cardiovascular events in high-risk individuals. In this randomized placebo-controlled human interventional trial, we aimed to evaluate whether Perilla frutescens leaf powder (PLP) ameliorates Ox-LDL and home blood pressure, along with its biological antioxidant potential. Healthy Japanese volunteers aged 30–60 years (n = 60) were randomized to PLP and placebo groups. The PLP group consumed PLP dried using a microwave under reduced pressure, and the placebo group consumed pectin fiber daily for 6 months. Home blood pressure, serum biochemical parameters, and fatty acid profiles of erythrocyte plasma membranes were analyzed. Plasma Ox-LDL levels significantly decreased in the PLP group but not in the placebo group. Mean changes in the biological antioxidant potential and alpha-linolenic acid levels in the erythrocyte plasma membrane were significantly increased in the PLP group than in the placebo group. In subjects with prehypertension (systolic blood pressure [SBP] ≥ 120 mmHg), the mean reduction in morning or nocturnal SBP was significantly greater in the PLP group than in the placebo group. Thus, PLP intake may be an effective intervention to prevent cardiovascular diseases.

Correlation of circulating ANGPTL5 levels with obesity, high sensitivity C-reactive protein and oxidized low-density lipoprotein in adolescents

Angiopoietin-like proteins (ANGPTL) is a family of eight members known to play an important role in metabolic diseases. Of these, ANGPTL5 is suggested to regulate triglyceride metabolism and is increased in obesity and diabetes. However, its role in metabolic diseases in adolescents is not well-studied. In this study, we tested the hypothesis of a positive association between plasma ANGPTL5, and obesity, high sensitivity C-reactive protein (HsCRP) and oxidized low-density lipoprotein (Ox-LDL) in adolescents. Adolescents (N = 431; age 11–14 years) were randomly selected from middle schools in Kuwait. Obesity was classified by the BMI-for-age based on the WHO growth charts. Plasma ANGPTL5, HsCRP, and Ox-LDL were measured using ELISA. The prevalence of overweight and obesity was 20.65% and 33.18%, respectively. Mean (SD) plasma ANGPTL5 levels were significantly higher in obese, compared with overweight and normal-weight adolescents (23.05 (8.79) vs 18.39 (7.08) ng/mL, and 18.26 (6.95) ng/ml, respectively). ANGPTL5 was positively associated with both HsCRP (ρ=0.27, p < 0.001) and Ox-LDL (ρ = 0.24, p < 0.001). In Conclusion, ANGPTL5 levels are elevated in obese adolescents and are associated with cardiovascular disease risk factors, HsCRP and Ox-LDL. The use of ANGPTL5 as a powerful diagnostic and prognostic tool in obesity and metabolic diseases needs to be further evaluated.

Association of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease

The association between oxidized low-density lipoprotein (OxLDL) and plaque instability in coronary and carotid artery disease is well established. However, the association between OxLDL and the histologic changes of plaque in peripheral artery disease has not been clearly elucidated. This study aims to investigate the association between plasma OxLDL and histologic plaque instability in patients with peripheral artery disease. Prospectively obtained plaques from 48 patients who underwent endovascular atherectomy (n=20), surgical endarterectomy (n=9), or bypass surgery (n=19) for treatment of atherosclerotic femoropopliteal artery disease were evaluated for histologic fibrosis, sclerosis, calcification, necrosis, cholesterol cleft, and foamy macrophages using hematoxylin and eosin, oil red O, and immunohistochemical staining. Unstable plaques were defined as plaques that were positive for foamy macrophages and with lipid content of more than 10% of the total plaque area. Plasma OxLDL levels were measured using an enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden). Of the 48 patients, 26 (54%) had unstable plaques. The unstable plaque group was younger, had fewer angiographic total occlusions, less calcification, and more CD68-positive and LOX-1-positive cells than the stable plaque group. Plasma OxLDL levels were significantly higher in the unstable plaque group than in the stable plaque group (57.4±13.9 vs. 47.2±13.6 U/L, P=0.014). Multivariate analysis revealed that plasma OxLDL level, smoking, angiographic nontotal occlusion, and statin nonuse were independent predictors of unstable plaque. Among patients with peripheral artery disease, the histologic instability of femoropopliteal plaque was independently associated with high plasma OxLDL, smoking, nontotal occlusion, and statin nonuse. Further large-scale studies are necessary to evaluate the role of noninvasive OxLDL measurement for predicting plaque instability and future adverse vascular event.

Therapeutic lifestyle change intervention improved metabolic syndrome criteria and is complementary to amlodipine/atorvastatin

AimsTo examine whether addition of amlodipine (5 mg)/atorvastatin (10 mg) A/A to Therapeutic Lifestyle change intervention (TLC) would beneficially modulate Metabolic Syndrome (MetS) and oxidized low-density lipoprotein (Ox-LDL) levels. MethodsPatients with MetS (n = 53) were randomized to TLC + placebo or TLC + A/A for 12 months. Anthropometric measurements, blood pressure (BP), lipid profile, plasma Ox-LDL, and area under the curve of free fatty acid (AUCFFA) during oral glucose tolerance test, a marker of adipose tissue health, were assessed before and after the intervention. ResultsTwenty-six patients completed the study with an overall improvement of MetS (p = 0.02). TLC + placebo was beneficial in reversing MetS comparable to TLC + A/A (54% vs. 39%; p = 0.08). Both treatments decreased systolic BP (p ≤ 0.01). TLC + A/A also decreased diastolic BP and triglyceride levels. The changes in Ox-LDL levels directly correlated with changes in weight in the TLC-placebo group (r = 0.64; p = 0.04). AUCFFA determined the loss of fat mass (r = 0.472, p = 0.03). Conclusions1) Addition of A/A has the advantage of improving the lipid profile and BP; but TLC alone was comparable to TLC + A/A in improving MetS; 2) weight change determines the TLC-associated change in Ox-LDL levels; and 3) AT metabolic health is a significant predictor of TLC-associated loss of body fat mass.

Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke

BackgroundAtrial fibrillation (AF) is a common cause of cerebral infarction, which could lead to endothelial dysfunction, increased reactive oxygen species (ROS) and oxidized low density lipoprotein (Ox-LDL).AF is associated with higher mortality and more severe neurologic disability. Statins may exert neuroprotective effects that are independent of LDL-C lowering. The purpose of our study was to investigate whether prestroke statins use could reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS).MethodsThis was a multicenter prospective study that involved four medical centers, 242 AIS patients with AF were identified, who underwent a comprehensive clinical investigation and a 72 h-Holter electrocardiogram monitoring. All patients were divided into two groups: prestroke statins use and no prestroke statins use groups, who were followed up for 3 months. Plasma Ox-LDL levels were measured using enzyme-linked immunosorbent assay (ELISA) on admission and at 3 months. The outcome was death, major disability (modified Rankin Scale score ≥ 3), and composite outcome (death/major disability) at 3 months after AIS.ResultsOne hundred thirty-six patients were in no prestroke statins use group, and 106 in prestroke statins use group. Plasma Ox-LDL levels were significantly lower in prestroke statins use than in no prestroke statins use on admission and at 3 months (P < 0.001). Plasma Ox-LDL levels on admission were associated with 3-month mortality [adjusted odds ratio (OR), 1.05; 95% confidence interval (CI), 0.99–1.12; P = 0.047]. In fully adjusted models, prestroke statins use was associated with reduced 3-month mortality [adjusted OR, 0.38; 95% CI, 0.16–0.91; P = 0.031)], major disability (adjusted OR, 0.38; 95% CI, 0.15–0.99; P = 0.047), and composite outcome (adjusted OR, 0.31; 95% CI, 0.17–0.74; P = 0.009).ConclusionsPrestroke statins use can reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related AIS.

Analysis of the correlation and diagnostic value of serum visfatin, hs-CRP and TNF-α in patients with different types of angina pectoris

Objective To explore the correlation and diagnostic value of serum visfatin (visfatin), high sensitive C reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) in patients with different types of angina pectoris. Methods Eighty-four patients with angina pectoris who were treated in the Eighth hospital of Wuhan from January 2013 to December 2016 were selected as the research subjects, the patients were divided into stable angina pectoris (SAP) group with 39 cases and unstable angina pectoris (UAP) group with 45 cases according to the classification criteria of angina pectoris, Thirty-seven healthy volunteers in the outpatient department of the same period were selected as the control group.To compare the levels of serum visfatin, hs-CRP and TNF-alpha in three groups, analyze the correlation between the levels of serum visfatin and hs-CRP and TNF-alpha levels in patients with angina pectoris, and analyze the diagnostic value of the levels of serum visfatin, hs-CRP, TNF-α and plasma oxidized low density lipoprotein (Ox-LDL) by ROC curve. Results There were no significant differences in fasting blood glucose, uric acid, creatinine, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) among the three groups (all P>0.05). The systolic pressure (SBP) was (134.27±11.96)mmHg and diastolic pressure (DBP) was (84.23±7.15)mmHg in SAP group, the SBP was (135.98±12.33)mmHg and DBP was (84.47±7.22)mmHg in UAP group, which were all higher than SBP ((121.49±9.97)mmHg )and DBP( (77.38±6.94)mmHg) in the control group (all P 0.05). The level of visfatin in UAP group was (6.57±1.36)μg/L, which was higher than that in SAP group( (4.62±1.08)μg/L) and in control group( (4.27±1.03)μg/L) (all P 0.05). The level of serum hs-CRP, TNF-α and plasma Ox-LDL were (12.38±2.63) mg/L, (4.35±0.28) ng/L and (617.32±53.48) μg/L in UAP group, and the level of serum hs-CRP, TNF-α and plasma Ox-LDL were (8.29±1.74) mg/L, (1.82±0.34)ng/L and (418.57±43.85)μg/L in SAP group, which were higher than hs-CRP (4.06±1.52) mg/L, TNF-α (0.98±0.13)ng/L, Ox-LDL (213.64±32.83)μg/L in control group(all P 0.05). The serum visfatin level was positively correlated with serum hs-CRP, TNF-alpha level and plasma Ox-LDL level in SAP group.(r=0.687, 0.634, 0.656, all P<0.05). The serum visfatin level was positively correlated with the serum hs-CRP, TNF-a level and Ox-LDL level in UAP group (r=0.721, 0.652, 0.673, all P<0.05). ROC curve analysis showed that the levels of serum visfatin, hs-CRP, TNF-α and plasma Ox-LDL were all near 0.7, and the sensitivity and specificity were all above 0.6 identification of different types of angina pectoris. Conclusion The level of serum visfatin in patients with UAP was significantly higher than that of SAP patients, its level is related to serum hs-CRP, TNF- alpha and plasma Ox-LDL levels, the four indexes have a certain predictive value for different types of angina pectoris, and can provide reference for different types of angina. Key words: Stable angina pectoris; Unstable angina pectoris; Visfatin; High sensitive C reactive protein; Tumor necrosis factorα

Associations of the PON1 rs662 polymorphism with circulating oxidized low-density lipoprotein and lipid levels: a systematic review and meta-analysis

BackgroundSeveral meta-analyses have demonstrated that the rs662 polymorphism in Paraoxonase 1 gene (PON1) gene is associated with coronary heart disease (CHD). However, it is still uncertain whether this polymorphism is associated with the plasma levels of oxidized low-density lipoprotein (Ox-LDL) and lipids. This meta-analysis is aimed to clarify the relationships between the rs662 polymorphism and plasma levels of Ox-LDL and lipids.MethodsBy searching in PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang, VIP and CNKI databases, 5 studies (1369 subjects) and 85 studies (46,740 subjects) were respectively identified for Ox-LDL association analysis and lipid association analysis. Standardized mean difference (SMD) was used to estimate the effects of the rs662 polymorphism on plasma Ox-LDL and lipid levels.ResultsThe carriers of the variant R allele had higher levels of Ox-LDL (SMD = 0.23, 95% CI = 0.10–0.36, P < 0.01), triglyceride (TG) (SMD = 0.06, 95% CI = 0.01–0.11, P = 0.02), total cholesterol (TC) (SMD = 0.04, 95% CI = 0.00–0.07, P = 0.05) and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.04, 95% CI = 0.00–0.08, P = 0.04) than the non-carriers.ConclusionsThis meta-analysis suggests that the association between the PON1 rs662 polymorphism and CHD may partly be mediated by abnormal Ox-LDL and lipid levels caused by the R allele.

The relationship between oxidized low-density lipoprotein and related ratio and acute cerebral infarction.

This study aimed to study the value of oxidized low-density lipoprotein (OX-LDL) and related ratio in the diagnosis of acute cerebral infarction and the classification of acute cerebral infarction.Of the 129 patients enrolled in this study, 94 patients with acute cerebral infarction were assigned to the case group, and 35 healthy subjects were enrolled as control group (n = 35). And then the case group were divided into large-artery atherosclerosis (LAA) group (n = 61) and small-artery occlusion (SAO) group (n = 33) according to the TOAST classification standard. Plasma OX-LDL levels were determined by enzyme-linked immunosorbent assay. OX-LDL/total cholesterol (OX-LDL/TC), OX-LDL/high-density lipoprotein (OX-LDL/HDL), OX-LDL/LDL were calculated.There were significant differences in OX-LDL, OX-LDL/TC, OX-LDL/HDL, and OX-LDL/LDL in patients with acute cerebral infarction and those in control group (P < .001). The area under the receiver-operating characteristic curve of OX-LDL and related ratio was >0.7 (P < .001). There was a slight positive correlation between OX-LDL/TC and National Institutes of Health Stroke Scale score at admission (r = 0.265, P = .039) in the LAA group.OX-LDL, OX-LDL/TC, OX-LDL/HDL, and OX-LDL/LDL were closely related to acute cerebral infarction, especially with large atherosclerotic cerebral infarction. OX-LDL/TC can reflect the severity of acute cerebral infarction for LAA, but it cannot predict the short-term prognosis of acute cerebral infarction.

Oxidative stress in obese children and adolescents with and without type 2 diabetes mellitus is not associated with obstructive sleep apnea.

Obesity, obstructive sleep apnea (OSA), and type 2 diabetes mellitus (T2DM) are associated with chronic low-grade inflammation and oxidative stress. In adults, increased lipid peroxidation, a marker of oxidative stress, was found in both metabolic syndrome and OSA. Studies on oxidative stress in children with T2DM and OSA are scarce. Plasma oxidized low-density lipoprotein (Ox-LDL) levels were evaluated in obese children and adolescents with/without T2DM, and the contribution of OSA to oxidative stress was investigated. Ten patients with T2DM, 8 with impaired glucose tolerance (IGT), and 20 body mass index-standard deviation score (BMI-SDS)-matched non-diabetic children (controls) were studied. They all underwent overnight polysomnography. Fasting plasma concentrations of Ox-LDL were measured and compared to the glycemic status and to the presence of OSA. Fourteen patients (36%) were diagnosed with OSA and 21 (55%) with hypertension. There were no significant group differences in plasma Ox-LDL levels or between patients with/without OSA. Plasma Ox-LDL levels were significantly higher among patients with hypertension compared to controls (P = 0.01), while they correlated with homeostasis model assessment (P = 0.02), BMI-SDS (P = 0.049), and systolic blood pressure (P = 0.002). The findings of this pilot study suggest that increased lipid peroxidation is associated with insulin resistance and hypertension in obese children and adolescents, while OSA has most likely minor influence.

Effect of 4-Week Ingestion of Tomato-Based Carotenoids on Exercise-Induced Inflammation, Muscle Damage, and Oxidative Stress in Endurance Runners.

This double-blind, randomized, placebo-controlled crossover trial determined if ingestion of a supplement containing a tomato complex with lycopene, phytoene, and phytofluene (T-LPP) and other compounds for 4 weeks would attenuate inflammation, muscle damage, and oxidative stress postexercise and during recovery from a 2-hr running bout that included 30min of -10% downhill running. Study participants ingested the T-LPP supplement or placebo with the evening meal for 4 weeks prior to running 2hr at high intensity. Blood samples and delayed onset muscle soreness ratings were taken pre- and post-4-week supplementation, and immediately following the 2-hr run, and then 1-hr, 24-hr, and 48-hr postrun. After a 2-week washout period, participants crossed over to the opposite treatment and repeated all procedures. Plasma lycopene, phytoene, and phytofluene increased significantly in T-LPP compared with placebo (p < .001 for each). Significant time effects were shown for serum creatine kinase, delayed onset muscle soreness, C-reactive protein, myoglobin, 9- and 13-hydroxyoctadecadienoic acids, ferric reducing ability of plasma, and six plasma cytokines (p < .001 for each). The pattern of increase for serum myoglobin differed between T-LPP and placebo (interaction effect, p = .016, with lower levels in T-LPP), but not for creatine kinase, delayed onset muscle soreness, C-reactive protein, the six cytokines, 9- and 13-hydroxyoctadecadienoic acids, and ferric reducing ability of plasma. No significant time or interaction effects were measured for plasma-oxidized low-density lipoprotein or serum 8-hydroxy-2'-deoxyguanosine. In summary, supplementation with T-LPP over a 4-week period increased plasma carotenoid levels 73% and attenuated postexercise increases in the muscle damage biomarker myoglobin, but not inflammation and oxidative stress.

Plasma nitric oxide and oxidized LDL levels in systemic lupus erythematosus (SLE)

Abstract Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with different clinical manifestations. The inflammatory and oxidative modification reactions are the most important events associated with cardiovascular complications of SLE patients. The aim of this study was to investigate the nitric oxide (NO) and the oxidized low-density lipoprotein (Ox-LDL) levels in order to explain the role of oxidized particles in development of clinical manifestations. Methods: A total of 80 subjects, SLE patients (n=40) and healthy controls (n=40), were recruited and matched regarding to age, gender, and body mass index (BMI). The biochemical parameters were measured using routine laboratory methods. The plasma Ox-LDL and NO levels were assayed with ELISA and colorimetric techniques, respectively. Results: The plasma NO level was significantly high in SLE patients (33.03±18.09 μmol/mL) in comparison to healthy controls (15.25±11.54 μmol/mL). In contrast, the total and normalized (Ox-LDL/LDL) plasma Ox-LDL values were low in SLE patients (p=0.2 and p&lt;0.05, respectively). A linear negative correlation was also observed between the plasma Ox-LDL and NO levels (r=0.25, p&lt;0.05). Multiple logistic regression analysis showed the critical role of NO on Ox-LDL level. Moreover, the disease activity and medications did not relate to the plasma Ox-LDL level (p&gt;0.5). Conclusions: The results showed that the excess NO prevents the oxidation of LDL particles so that the inflammatory events in comparison to oxidative modifications may be most involved in clinical complications of SLE patients.

Diet-induced increase in plasma oxidized LDL promotes early fibrosis in a renal porcine auto-transplantation model

BackgroundIn kidney transplantation, the prevalence of hypercholesterolemia as a co-morbidity factor known to affect graft function, is rising due to the increased number of older donors in response to organ shortage as well as to the hyperlipidemic effects of immunosuppressors in recipient. This study aimed to characterize the effects of hypercholesterolemia on renal graft outcome, investigating the role of oxidized low-density lipoprotein (OxLDL).MethodsIn vivo, we used a porcine preclinical model of renal auto-transplantation modulated by two experimental diets: a normal (n = 6) or a hyperlipidemic diet (n = 5) maintained during the 3 month follow-up after the surgical procedure. Kidney function and OxLDL levels were monitored as well as fibrosis, LOX-1 and TGF beta signaling pathways. In vitro, we used human artery endothelial cells subjected to OxLDL to investigate the TGF beta profibrotic pathway and the role of the scavenger receptor LOX-1.ResultsHyperlipidemic diet-induced increase in plasma OxLDL levels at the time of surgery correlated with an increase in proteinuria 3 months after transplantation, associated with an early graft fibrosis combined with an activation of renal TGF beta signaling. These data suggest a direct involvement of OxLDL in the hyperlipidemic diet-induced activation of the pro-fibrotic TGF beta pathway which seems to be activated by LOX-1 signaling. These results were supported by studies with endothelial cells incubated in culture medium containing OxLDL promoting TGF beta expression inhibited by LOX-1 antibody.ConclusionsThese results implicate OxLDL in the hyperlipidemic diet-promoted fibrosis in transplanted kidneys, suggesting LOX-1 as a potential therapeutic target and reinforce the need to control cholesterol levels in kidney transplant recipients.

Effect of Glycemic Control on Plasma Oxidized Low Density Lipoprotein Levels in Diabetics

Objective: Increased low-density lipoprotein (LDL) glycation in diabetics could facilitate LDL oxidation, which is proatherogenic. I studied plasma oxidized LDL (OxLDL) levels in diabetics and non-diabetics, their relation to glycemic control, and their circadian variations. Methods: OxLDL in diabetics (n=32) and in non-diabetics without coronary artery diseases (n=20) were compared. OxLDL in diabetics (n=24) was measured on Days 2, 3, 4, 8 and the last day of hospitalization. Circadian variation in OxLDL in diabetics (n=18) was also examined. Glycemic control was implemented during hospitalization. Patients: The diabetics were divided into two groups; moderately-controlled (MC) group (HbA1c < 9.0% at admission, n = 15) and poorly-controlled (PC) group (HbA1c ≧ 9.0% at admission, n = 9). Results： In the MC group, OxLDL decreased by 20.8% after glycemic control (p = 0.0139), but not in the PC group. OxLDL is correlated with LDL on Days 3, 4, 8 (r = 0.837, 0.864, 0.801, respectively), TG on Day 8(r = 0.932), and Lp(a) at discharge (r = 0.871). In the PC group, OxLDL was 15.8% higher on the average in the daytime than at night (p = 0.0024). Conclusion： Plasma OxLDL is decreased by glycemic control, particularly in moderately glycemic controlled patients. OxLDL has a circadian variation, particularly in poorly glycemic controlled patients. Long-term glycemic control could reduce the progression of atherosclerosis, by reducing OxLDL levels.

Involvement of toll-like receptor 2 and 4 in association between dyslipidemia and osteoclast differentiation in apolipoprotein E deficient rat periodontium

BackgroundDyslipidemia increases circulating levels of oxidized low-density lipoprotein (OxLDL) and this may induce alveolar bone loss through toll-like receptor (TLR) 2 and 4. The purpose of this study was to investigate the effects of dyslipidemia on osteoclast differentiation associated with TLR2 and TLR4 in periodontal tissues using a rat dyslipidemia (apolipoprotein E deficient) model.MethodsLevels of plasma OxLDL, and the cholesterol and phospholipid profiles in plasma lipoproteins were compared between apolipoprotein E-deficient rats (16-week-old males) and wild-type (control) rats. In the periodontal tissue, we evaluated the changes in TLR2, TLR4, receptor activator of nuclear factor kappa B ligand (RANKL) and tartrate resistant acid phosphatase (TRAP) expression.ResultsApolipoprotein E-deficient rats showed higher plasma levels of OxLDL than control rats (p<0.05), with higher plasma levels of total cholesterol (p<0.05) and LDL-cholesterol (p<0.05) and lower plasma levels of high-density lipoprotein cholesterol (p<0.05). Their periodontal tissue also exhibited a higher ratio of RANKL-positive cells and a higher number of TRAP-positive osteoclasts than control rats (p<0.05). Furthermore, periodontal gene expression of TLR2, TLR4 and RANKL was higher in apolipoprotein E-deficient rats than in control rats (p<0.05).ConclusionThese findings underscore the important role for TLR2 and TLR4 in mediating the osteoclast differentiation on alveolar bone response to dyslipidemia.

Fenofibrate Improves Vascular Endothelial Function by Reducing Oxidative Stress While Increasing Endothelial Nitric Oxide Synthase in Healthy Normolipidemic Older Adults

Vascular endothelial dysfunction develops with aging, as indicated by impaired endothelium-dependent dilation, and is related to increased cardiovascular disease risk. We hypothesized that short-term treatment with fenofibrate, a lipid-lowering agent with potential pleiotropic effects, would improve endothelium-dependent dilation in middle-aged and older normolipidemic adults by reducing oxidative stress. Brachial artery flow-mediated dilation, a measure of endothelium-dependent dilation, was assessed in 22 healthy adults aged 50 to 77 years before and after 7 days of fenofibrate (145 mg/d; n=12) or placebo (n=10). Brachial flow-mediated dilation was unchanged with placebo, but improved after 2 and 7 days of fenofibrate (5.1±0.7 versus 2 days: 6.0±0.7 and 7 days: 6.4±0.6%δ; both P &lt;0.005). The improvements in flow-mediated dilation after 7 days remained significant ( P &lt;0.05) after accounting for modest changes in plasma total and low-density lipoprotein cholesterol. Endothelium-independent dilation was not affected by fenofibrate or placebo ( P &gt;0.05). Intravenous infusion of the antioxidant vitamin C improved brachial flow-mediated dilation at baseline in both groups and during placebo treatment ( P &lt;0.05), but not after 2 and 7 days of fenofibrate ( P &gt;0.05). Fenofibrate treatment also reduced plasma-oxidized low-density lipoprotein, a systemic marker of oxidative stress, compared with placebo ( P &lt;0.05). In vascular endothelial cells sampled from peripheral veins of the subjects, endothelial nitric oxide synthase protein expression was unchanged with placebo and after 2 days of fenofibrate, but was increased after 7 days of fenofibrate (0.54±0.03 versus 2 days: 0.52±0.04 and 7 days: 0.76±0.11 intensity/human umbilical vein endothelial cell control; P &lt;0.05, 7 days). Short-term treatment with fenofibrate improves vascular endothelial function in healthy normolipidemic middle-aged and older adults by reducing oxidative stress and induces an increase in endothelial nitric oxide synthase.