oxLDL Levels Research Articles

AIM2 regulates vascular smooth muscle cell migration in atherosclerosis

BackgroundAtherosclerosis (AS) is a common pathological basis of various cardiovascular and cerebrovascular diseases. Plaque formation is initiated and triggered by vascular smooth musclecells (VSMCs) migration in vascular wall, which gradually aggravates atherosclerosis progression. Absent in melanoma 2 (AIM2), a member of HIN-200 family, plays an important role in activating inflammasome. However, the role of AIM2 in atherosclerotic plaque progression outside of the inflammasome has not yet been reported. MethodsThe potential effect and the underlying mechanism of AIM2 were investigated in apoliporotein E-deficient (ApoE−/−) mice. Murine AIM2 lentivirus, shRNA-AIM2 lentivirus and null lentivirus were constructed and injected intravenously into ApoE−/− mice, which were fed on a high fat diet. The specific mechanism of AIM2 in vascular smooth cells (VSMCs) was explored in vitro. ResultsResults showed the aortic atherosclerotic lesion area was larger with AIM2 over-expression, and the number of smooth muscle cells was enhanced in line with the increased AIM2 levels. AIM2 overexpression also induced the increasing expression of MMP2. In vitro studies revealed that different levels of ox-LDL increased AIM2 expression in a time–dependent manner. Transwell showed that AIM2 mediated migration in VSMCs. The expression of AIM2 can be inhibited when the ROS inhibitor was used. Additionally, the overexpression and inhibition of AIM2 significantly affects HG-induced migration and TGF-β/SMAD signaling pathway in VSMCs. ConclusionThus, we demonstrated that AIM2 could promote the progression of atherosclerotic plaque by increasing migration in VSMCs.

The relationship between oxidized low-density lipoprotein and the NIHSS score among patients with acute ischemic stroke: The SOS-Stroke Study

Background and aimsOxidized low-density lipoprotein (oxLDL) has a defined role in the genesis and development of atherosclerosis, however, whether it is related to severity of neurological deficits is rarely reported. The aim of our study was to investigate the potential association between oxLDL and the National Institutes of Health Stroke Scale (NIHSS) score among patients with acute ischemic stroke. MethodsBetween January 2014 and October 2014, we recruited 4111 patients with acute ischemic stroke (AIS), who were admitted within 7 days–43 hospitals in China, and participated in the SOS-Stroke Study. We collected detailed clinical data and then tested the relationship between oxLDL and the NIHSS score using a multivariate linear regression analysis. ResultsAfter adjusting for age, gender, ethnicity, marriage and other confounding variables, the elevated NIHSS score was significantly associated with increased oxLDL levels, and each 1-μg/dL elevation in oxLDL concentration resulted in an increase of 0.027 in the NIHSS score. ConclusionsA positive correlation was found between plasma levels of oxLDL and the NIHSS score in patients with acute ischemic stroke. Higher plasma levels of oxLDL potentially suggest a worse prognosis in AIS patients.

Abstract TMP114: Oxidized Low Density Lipoprotein Predicts Recurrent Stroke in Patients With Minor Stroke or Transient Ischemic Attack

Introduction: Elevated oxidized low-density lipoprotein (oxLDL) was shown to be related to atherosclerotic cardiovascular diseases, but the role of oxLDL in predicting recurrent stroke in patients with minor stroke or transient ischemic attack remains unclear. We aimed to investigate the association between oxLDL and recurrent stroke. Methods: In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, baseline oxLDL levels were measured. The primary outcomes were any stroke within 90 days and 1 year. The association of oxLDL with recurrent stroke was analyzed by using Cox proportional hazards model. Results: Among the 3019 patients included in this study, the median (IQR) of oxLDL was 13.96 (6.65-28.81) ug/dl. After adjusted for conventional confounding factors, patients in the highest oxLDL quartile had a higher risk of recurrent stroke within 90 days (HR, 1.42; 95% CI, 1.02-1.96) and 1 year (HR, 1.41; 95% CI, 1.05-1.90) compared with the lowest oxLDL quartile. There was no significant interaction between oxLDL levels and randomized antiplatelet therapy. Conclusions: Elevated oxLDL levels can independently predict recurrent stroke in patients with minor stroke or transient ischemic attack.

LOX-1 deficient mice show resistance to zymosan-induced arthritis.

Recent data suggest that the lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system may be involved in the pathogenesis of arthritis. We aimed to demonstrate the roles of the LOX- 1/ox-LDL system in arthritis development by using LOX-1 knockout (KO) mice. Arthritis was induced in the right knees of C57Bl/6 wild-type (WT) and LOX-1 KO mice via zymosan injection. Saline was injected in the left knees. Arthritis development was evaluated using inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration scores at 1, 3, and 7 days after administration. LOX-1, ox-LDL, and matrix metalloproteinase-3 (MMP-3) expression in the synovial cells and chondrocytes was evaluated by immunohistochemistry. The LOX-1, ox-LDL, and MMP-3 expression levels in synovial cells were scored on a grading scale. The positive cell rate of LOX-1, ox-LDL, and MMP-3 in chondrocytes was measured. The correlation between the positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score was also examined. Inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration were significantly reduced in the LOX-1 KOmice with zymosan-induced arthritis (ZIA) compared to WT mice with ZIA. In the saline-injected knees, no apparent arthritic changes were observed. LOX-1 and ox-LDL expression in synovial cells and chondrocytes were detected in the knees of WT mice with ZIA. No LOX-1 and ox-LDL expression was detected in the knees of LOX-1 KO mice with ZIA or the salineinjected knees of both mice. MMP-3 expression in the synovial cells and chondrocytes was also detected in knees of both mice with ZIA, and was significantly less in the LOX-1 KO mice than in WT mice. The positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score showed a positive correlation. Our data show the involvement of the LOX-1/ox-LDL system in murine ZIA development. LOX-1-positive synovial cells and chondrocytes are potential therapeutic targets for arthritis prevention.

Thrombomodulin as a New Marker of Endothelial Dysfunction in Chronic Kidney Disease in Children.

Endothelial dysfunction (ED) and oxidative stress are potential new pathomechanisms of cardiovascular diseases in patients with chronic kidney disease (CKD). The aim of the study was to assess the association between endothelial dysfunction, oxidative stress biomarkers, and cardiovascular risk factors in children with CKD. Serum oxidized LDL (oxLDL), protein carbonyl group, urea, creatinine, cystatin C, thrombomodulin, asymmetric dimethylarginine (ADMA), von Willebrand factor, brain natriuretic peptide (BNP), lipids, high sensitivity C-reactive protein, intercellular adhesion molecule-1 levels, and albuminuria were measured. Anthropometric, ambulatory blood pressure (BP) measurements and echocardiography were performed. The studied group consisted of 59 patients aged 0.7–18.6 (mean 11.1) years with stages 1 to 5 CKD. Thrombomodulin strongly correlated with creatinine (R = 0.666; p < 0.001), cystatin C (R = 0.738; p < 0.001), BNP (R = 0.406; p = 0.001), ADMA (R = 0.353; p = 0.01), oxLDL (R = 0.340; p = 0.009), 24-hour systolic (R = 0.345; p = 0.011) and mean (R = 0.315; p < 0.05) BP values, and left ventricular mass index (LVMI, R = 0.293; p = 0.024) and negatively with estimated glomerular filtration rate (R = −0.716; p < 0.001). In children with CKD, TM strongly depended on kidney function parameters, oxLDL levels, and 24-hour systolic and mean BP values. Thrombomodulin seems to be a valuable marker of ED in CKD patients, correlating with CKD stage as well as oxidative stress, BP values, and LVMI.

OLR1 Gene Polymorphism and Oxidized LDL Levels in Metabolic Syndrome in Indian Population.

Objective:Metabolic syndrome (MetS) is associated with abnormal lipid profile and high cardiovascular risk. There is an increased prevalence of coronary artery disease and Type 2 Diabetes Mellitus in India. Oxidized Low Density Lipoprotein Receptor 1(OLR1), a cell surface endocytosis receptor recognize, internalize and degrade oxidized LDL (oxLDL) in vascular endothelium and plays a role in the pathogenesis of atherosclerosis. The aim was to explore the association of OLR1 gene polymorphism and measure the serum levels of ox-LDL in patients with MetS in Indian population.Materials and Methods:Forty cases fulfilling the IDF diagnostic criteria for MetS and 40 healthy controls having similar age and sex ratio were genotyped for OLR1 gene (SNP: IVS4–73C>T , rs3736234) by RFLP-PCR. Serum ox-LDL was estimated by ELISA.Their BP, BMI and waist circumference were measured. Fasting Plasma glucose, Serum Triglyceride and HDL-C were measured.Results:Serum oxLDL was significantly higher in MetS cases as compared to controls (p < 0.0001). Odds ratio of T allele of above OLR1 SNP among subjects with MetS was 14.79 (95%CI: 1.80-121.2, p < 0.05). But no association was found between the SNP and serum ox-LDL levels. People having TT allele had higher BMI compared to those having CC allele.Conclusion:Ox LDL, being more atherogenic might contribute in the pathogenesis of MetS. The intronic SNP: IVS4-73 C>T of OLR1 gene increases the risk of developing MetS by a yet unknown mechanism that is independent of rise in ox-LDL. This OLR1 SNP probably influences BMI.

Anti-Atherogenic Activity of Polyphenol-Rich Extract from Bee Pollen.

The aim of this study was to determine the effect of polyphenol-rich ethanol extract of bee pollen (EEP) on atherosclerosis induced by a high-fat diet in ApoE-knockout mice. EEP was given with feed in two doses of 0.1 and 1 g/kg body mass (BM). The studies have been conducted in a period of 16 weeks. The following factors were estimated: total cholesterol (TC), oxidized low density lipoproteins (ox-LDL), asymmetric dimethylarginine (ADMA), angiotensin-converting enzyme (ACE) and angiotensin II (ANG II) in the 5th, 10th, 12th, 14th, and 16th week of the experiment. In the last, i.e., 16th week of the studies the development of coronary artery disease (CAD) was also estimated histopathologically. Supplementing diet with EEP resulted in decreasing TC level. EEP reduced oxidative stress by lowering the levels of ox-LDL, ADMA, ANG II and ACE. EEP protected coronary arteries by significantly limiting the development of atherosclerosis (the dose of 0.1 g/kg BM) or completely preventing its occurrence (the dose of 1 g/kg BM). The obtained results demonstrate that EEP may be useful as a potential anti-atherogenic agent.

Oxidized Low-Density Lipoprotein and Cell Adhesion Molecules Following Exercise Training.

Elevated oxidized low-density lipoprotein (ox-LDL) and cell adhesion molecules are associated with inflammation and atherosclerosis. The role of exercise in circulating ox-LDL, enzyme mediators, and cell adhesion molecules are not clearly understood in obesity. As a randomized controlled design, 27 obese (BMI>30 kg/m2) sedentary men (N=13) and women (N=14) were randomly assigned to either an exercise (N=15) or a control (N=12) group. The exercise group performed a 60-min supervised treadmill exercise at moderate intensity (70% of HRmax) for 3 days per week for 4 weeks, while the control group did not exercise. Overnight fasting blood samples were collected before and after the study period to analyze serum lipids, lipoprotein-cholesterol, ox-LDL, 12- and 15-lipoxygenases, myeloperoxidase (MPO), and soluble vascular cell adhesion molecules-1 and intercellular adhesion molecule-1. Moderate-intensity exercise training lowered both ox-LDL (from 44.76±1.99 to 38.51±1.99 U/L, p=0.032) and MPO (from 31.48±2.20 to 23.09±2.20 ng/mL, p=0.010), without significantly altering body weight, other parameters of serum lipids and lipoproteins, or soluble cell adhesion molecules. Moderate intensity exercise training reduced the levels of ox-LDL and MPO, indicating a reduced risk for developing CVD and additional protection to the possible metabolic complications associated with obesity.

Lipoprotein-associated phospholipase A2 and oxidized low-density lipoprotein in young patients with acute coronary syndrome in China

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered to be a risk factor for acute coronary syndrome (ACS), but this remains controversial. This study investigated the role of Lp-PLA2 in young Chinese patients with ACS. 228 young patients (aged ≤55 years) with ACS and 237 age-matched controls were included. Lp-PLA2 and oxidized low-density lipoprotein (ox-LDL) levels were measured by sandwich enzyme-linked immunosorbent assay. Lp-PLA2 levels were significantly correlated with smoking, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ox-LDL levels (all P < 0.05). Multivariate logistic regression analysis showed that male sex (OR = 3.25, 95%CI = 1.26–8.38), smoking (OR = 3.50, 95%CI = 1.75–7.0), triglyceride (OR = 1.76, 95%CI = 1.08–2.87), high sensitivity C-reactive protein (hs-CRP) (OR = 2.11, 95%CI = 1.14–3.90) and ox-LDL (OR = 2.98, 95%CI = 1.72–5.1) were independently associated with ACS risk in young patients. Lp-PLA2 was associated with risk of ACS in young patients when adjusted for traditional risk factors, including age, sex, diabetes, hypertension, smoking, TC, LDL-C, triglyceride and hs-CRP (OR = 1.98, 95%CI = 1.10–3.56). When further adjusted for ox-LDL levels, the association between Lp-PLA2 and ACS became insignificant (OR = 1.69, 95%CI = 0.90–3.17). Lp-PLA2 was a marker of oxidative stress and inflammation, rather than an independent risk factor for ACS in young Chinese patients.

Association between oxidized low‐density lipoprotein and cognitive impairment in patients with ischemic stroke

The association between oxidized low-density lipoprotein (oxLDL) and cognitive impairment is unclear. This study aimed to investigate the potential association between oxLDL and cognitive impairment among patients with acute ischemic stroke. We measured the levels of oxLDL and recorded the Mini-Mental State Examination (MMSE) score in patients with acute ischemic stroke who were recruited from the Study of Oxidative Stress in Patients with Acute Ischemic Stroke. Cognitive impairment was defined as an MMSE score of <24. The association between oxLDL and cognitive impairment was assessed by multivariate logistic or linear regression analysis. Other clinical variables of interest were also studied. A total of 3726 patients [1287 (34.54%) female] were included in this study, with a mean age of 63.62±11.96years. After adjusting for potential confounders in our logistic regression model, each SD increase in oxLDL was associated with a 26% increase in the prevalence of cognitive impairment (odds radio, 1.26; 95% confidence interval, 1.13-1.39; P<0.0001). Similarly, higher oxLDL was associated with lower MMSE scores, with a 0.56-point decrease in MMSE score for every SD increase in oxLDL in a linear regression analysis (β=-0.56; 95% confidence interval, -0.81 to -0.32; P<0.0001). There were no significant interactions between oxLDL and age, sex or education levels for cognitive impairment (all interactions, P>0.05). Elevated levels of oxLDL were associated with a higher prevalence of cognitive impairment in patients with ischemic stroke.

LOX-1 activation by oxLDL triggers an epithelial mesenchymal transition and promotes tumorigenic potential in prostate cancer cells

Obesity is related to an increased risk of developing prostate cancer with high malignancy stages or metastasis. Recent results demonstrated that LOX-1, a receptor associated with obesity and atherosclerosis, is overexpressed in advanced and metastatic prostate cancer. Furthermore, high levels of oxLDL, the main ligand for LOX-1, have been found in patients with advanced prostate cancer. However, the role of LOX-1 in prostate cancer has not been unraveled completely yet. Here, we show that LOX-1 is overexpressed in prostate cancer cells and its activation by oxLDL promotes an epithelial to mesenchymal transition, through of lowered expression of epithelial markers (E-cadherin and plakoglobin) and an increased expression of mesenchymal markers (vimentin, N-cadherin, snail, slug, MMP-2 and MMP-9). Consequently, LOX-1 activation by oxLDL promotes actin cytoskeleton restructuration and MMP-2 and MMP-9 activity inducing prostate cancer cell invasion and migration. Additionally, LOX-1 increased the tumorigenic potential of prostate cancer cells and its expression was necessary for tumor growth in nude mice. In conclusion, our results suggest that oxLDL/LOX-1 could be ones of mechanisms that explain why obese patients with prostate cancer have an accelerated tumor progression and a greater probability of developing metastasis.

Potential of Metformin to Improve Cardiac Risk in Postpartum Women with Gestational Diabetes.

Pregnancy is associated with an increase in total cholesterol, high density lipoproteins (HDL), and low-density lipoproteins (LDL). Postpartum, HDL and LDL decrease over the first 12 weeks postpartum. Oxidized LDL (ox-LDL) is a marker of oxidative stress-related inflammation, which is associated with obesity and also with development of cardiovascular disease. Cardiovascular protection and weight loss are benefits from metformin, especially in women with diabetes. The objective of this study was to compare changes in lipid profiles and biomarkers for obesity during the initial 6 weeks postpartum between women with gestational diabetes mellitus (GDM) treated with metformin versus placebo. This was a planned ancillary study of a randomized controlled trial compares metformin versus placebo in women with GDM for postpartum weight loss. Two 3 mL blood samples were collected within 24 h of delivery and 6 weeks postpartum immediately processed after collection then stored at -20°C until completion of clinical trial prior to analysis. Change in the median plasma concentrations of total cholesterol, HDL, ox-LDL, glucose, insulin, leptin, and unacylated ghrelin were compared between study groups. Of the 77 postpartum women were included, 35 received metformin and 42 received placebo. There was less of a reduction in HDL in the metformin group compared to placebo (-2.3 versus -7.5 mg/dL, p = 0.019). In addition, there was a greater reduction in ox-LDL in those receiving metformin (-12.2 versus -3.8 mg/dL, p = 0.038). No other differences were observed in the selected biomarkers evaluated. Biomarker levels of HDL and ox-LDL were positively affected during the initial 6 weeks postpartum in GDM women treated with metformin. Additional studies with a longer duration of metformin treatment in the postpartum period are warranted to evaluate long-term potential benefits.

Atorvastatin inhibits cholesterol-induced caspase-3 cleavage through down-regulation of p38 and up-regulation of Bcl-2 in the rat carotid artery.

SummaryAim:Atherosclerotic lesions in the carotid arteries lead to a broad range of cerebrovascular disorders such as vascular dementia and ischaemic stroke. Recent studies have verified the beneficial role of atorvastatin (AV) in atherosclerosis. Despite a large body of studies, the mechanisms underlying this effect have not been completely explained. In this study, several experiments were performed on atherosclerotic rat models to investigate the anti-inflammatory and anti-apoptotic effect of AV in the carotid artery.Methods:In this experimental study, 40 male Wistar rats (250 ± 25 g) were randomly divided into four groups: rats on a normal diet (ND; n = 10); a high-cholesterol diet (HD; n = 10); a high-cholesterol diet plus AV (HD + AV; n = 10); and the AV control group (AV; n = 10). Cleavage of caspase-3 protein, expression of B-cell lymphoma 2 (Bcl-2) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) were determined by immunoblotting assay in the carotid artery homogenate. Plasma atherogenic indices, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured by colorimetric assay at the end of the experiment. Plasma levels of oxidised LDL (oxLDL) were measured by sandwich enzyme-linked immunosorbent assay (ELISA).Results:After eight weeks of feeding with a high-cholesterol diet, an elevated level of oxLDL was observed in the plasma in the HD group compared with the ND group [214.42 ± 17.46 vs 69.13 ± 9.92 mg/dl (5.55 ± 0.45 vs 1.78 ± 0.26 mmol/l); p < 0.01]. AV administration significantly reduced oxLDL levels in the HD + AV compared to the HD group [126.52 ± 9.46 vs 214.42 ± 17.46 mg/dl (3.28 ± 0.25 vs 5.55 ± 0.45 mmol/l); p < 0.01]. Results also showed that compared with the HC group, the HC + AV group had lower levels of p38 phosphorylation (p < 0.05) and higher levels of Bcl-2 expression (p < 0.05). Lower levels of cleaved caspase-3 were observed in the HC + AV group in comparison with the HC group (p < 0.05).Conclusions:The resultant data suggest that the anti-apoptotic effect of AV could be partially mediated by the pro-inflammatory protein p38 MAPK and the anti-apoptotic protein Bcl-2 in the rat carotid artery. Atorvastatin can therefore be considered a target drug in the prevention or development of atherosclerotic events.

Association of Lp‐PLA2 G994T gene polymorphism with risk of ischemic stroke in Chinese population

The association between lipoprotein-associated phospholipase A2 (Lp-PLA2) G994T gene polymorphism and the risk of ischemic stroke is unclear. The aim of this study is to investigate the influence of Lp-PLA2 G994T genetic variant on the pathogenesis of ischemic stroke in Chinese population. A total of 348 patients with a clinical diagnosis of ischemic stroke and 260 gender-matched control subjects under physical examination were recruited from hospitals and genotyped for G994T gene polymorphism. The results showed that there was a significant difference in the genotype distribution between the two groups and people with GT or TT genotype were associated with the higher risk of ischemic stroke even after adjusting the effects of potential confounding factors. In addition, both ischemic stroke patients and control subjects carrying T allele showed relatively lower Lp-PLA2 activity and higher oxLDL level. Therefore, Lp-PLA2 G994T gene polymorphism may be an independent risk factor of ischemic stroke in Chinese population.

Combined supplementation with α-tocopherol and vitamin C improves the blood pressure of pediatric idiopathic nephrotic syndrome patients

Summary The purpose of the present study was to investigate the effects of combined supplementation with α-tocopherol and vitamin C on blood pressures and levels of ox-LDL and NOx in with pediatric idiopathic nephrotic syndrome patients. A total of thirty-six pediatric idiopathic nephrotic syndrome patients was involved in the study, which was assigned randomly into two groups, the control group of pediatric idiopathic nephrotic syndrome patients who received a standard therapy and placebo and the group of pediatric idiopathic nephrotic syndrome patients who received a standard therapy plus α-tocopherol and vitamin C. α-tocopherol and vitamin C were administered at a dose of 10–15 mg/kg/day for 12 weeks. An analysis of lipid profile and NOx was performed by means of a spectrophotometer. An analysis of ox-LDL was performed by using the enzyme-linked immunosorbent assay technique. There was a significant decrease in the number of prehypertensive and hypertensive patients in the supplementation group relative to the control group (p 0.50). In conclusion, the combined supplementation with α-tocopherol and vitamin C may improve blood pressure in pediatric idiopathic nephrotic syndrome patients. Thus, combination of α-tocopherol and vitamin C can be used in the clinical management of pediatric idiopathic nephrotic syndrome.

Oxidized low-density lipoprotein (oxLDL) affects load-free cell shortening of cardiomyocytes in a proprotein convertase subtilisin/kexin 9 (PCSK9)-dependent way

Recent studies have documented that oxidized low-density lipoprotein cholesterol (oxLDL) levels directly impact myocardial structure and function. However, the molecular mechanisms by which oxLDL affects cardiac myocytes are not well established. We addressed the question whether oxLDL modifies load-free cell shortening, a standardized readout of cardiac cellular function, and investigated whether proprotein convertase subtilisin/kexin-9 (PCSK9) is involved on oxLDL-dependent processes. Adult rat ventricular cardiomyocytes were isolated and incubated for 24 h with oxLDL. PCSK9 was silenced by administration of siRNA. Load-free cell shortening was analyzed via a line camera at a beating frequency of 2 Hz. RT-PCR and immunoblots were used to identify molecular pathways. We observed a concentration-dependent reduction of load-free cell shortening that was independent of cell damage (apoptosis, necrosis). The effect of oxLDL was attenuated by silencing of oxLDL receptors (LOX-1), blockade of p38 MAP kinase activation, and silencing of PCSK9. oxLDL increased the expression of PCSK9 and caused oxidative modification of tropomyosin. In conclusion, we found that oxLDL significantly impaired contractile function via induction of PCSK9. This is the first report about the expression of PCSK9 in adult terminal differentiated ventricular cardiomyocytes. The data are important in the light of recent development of PCSK9 inhibitory strategies.

Oxidative stress induced modulation of platelet integrin α2bβ3 expression and shedding may predict the risk of major bleeding in heart failure patients supported by continuous flow left ventricular assist devices

IntroductionOxidative stress and platelet integrin α2bβ3 plays important role in the process of hemostasis and thrombosis. We hypothesized that device-induced patient specific oxidative stress and integrin α2bβ3 shedding may be linked to major bleeding complication (MBC) in heart failure (HF) patients supported by continuous flow left ventricular assist devices (CF-LVADs). Materials and methodsWe recruited 47patients implanted with CF-LVADs and 15 healthy volunteers. Fourteen patients developed MBC (bleeder group) within one month after implantation while others were considered non-bleeder group (n=33). Oxidative stresses were evaluated by measuring reactive oxygen species (ROS) in platelets, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) and oxidized low density lipoprotein (oxLDL). Assessments of α2bβ3 were carried out using flow cytometry and ELISA. ResultsBiomarkers of oxidative stress and α2bβ3 shedding (decreased surface expression and higher plasma levels) were found to be preexisting condition in all HF patients prior to CF-LVAD implantation compared to the healthy volunteers. Significantly elevated levels of ROS and oxLDL; concomitant depletion of SOD and TAC; and α2bβ3 shedding were observed in the bleeder group temporarily in comparison to the non-bleeder group after CF-LVAD implantation. A significantly strong association between α2bβ3 shedding and biomarkers of oxidative stress was observed; suggesting a potential role of oxidative stress in platelet integrin shedding leading to MBC after CF-LVAD implantation. Moreover, a receiver operating characteristic (ROC) analysis indicated that the likelihood of MBC data from Integrin α2bβ3 shedding had a predictive power of MBC in CF-LVAD patients. ConclusionsOxidative stress might play a potential role in accelerating α2bβ3 shedding and platelet dysfunction, resulting in MBC in CF-LVAD patients. Integrin α2bβ3 shedding may be used to refine bleeding risk stratification in CF-LVAD patients.

Influence of serum HMW adiponectin level in patients with pregnancy-induced hypertension syndrome on the occurrence of eclampsia in secondary pregnancy.

In the present study, we studied the influence of serum high-molecular weight adiponectin (HMWA) levels in patients with pregnancy-induced hypertension (PIH) on the occurrence of eclampsia in secondary pregnancy and its related mechanisms. In total, 130 patients who were diagnosed with PIH for the first time were selected for this study; the median interval of the secondary pregnancy was 28.5 months. The serum HMWA and leptin levels both times were detected, and the insulin resistance indexes (HOMA-IR) were calculated. The serum inflammatory indexes in the secondary pregnancy included interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and the oxidative stress indexes included methane dicarboxylic aldehyde (MDA) and oxidized low-density lipoprotein (ox-LDL) levels. The expression levels of adiponectin receptor 2 and cyclooxygenase-2 (COX-2) in placental tissue were detected. In secondary pregnancy, there were a total of 20 cases of eclampsia (15.38%), including 2 cases of mild PIH, 8 cases of moderate PIH and 10 cases of severe PIH; differences were statistically significant when compared to patients without eclampsia (p<0.001). The serum HMWA levels in patients with severe PIH in the first pregnancy were significantly lower than those in patients with mild and moderate PIH, and the serum levels in patients with mild PIH were the highest. The leptin levels in patients with severe PIH were significantly higher than those in patients with mild and moderate PIH, and the leptin levels in patients with mild PIH were the lowest (p<0.05). The HMWA levels in patients with eclampsia in the secondary pregnancy was significantly lower than those in patients without eclampsia, and the leptin levels in patients with eclampsia were significantly increased. The HMWA levels in patients with eclampsia in the secondary pregnancy were lower than that in the first pregnancy, whereas the leptin levels were higher than that in the first pregnancy (p<0.05). HOMA-IR, IL-6, TNF-α, MDA and ox-LDL levels in patients with eclampsia were significantly higher than those in patients without eclampsia (p<0.05), and the adiponectin receptor 2 and COX-2 expression levels in the placental tissue were significantly higher than those in patients without eclampsia (p<0.05). Therefore, the serum HMWA levels are closely related to the occurrence of eclampsia in PIH patients in secondary pregnancy, and it influences insulin resistance, inflammatory response and oxidative stress response, which is correlated with increased adiponectin receptor 2 and COX-2 protein expression in placental tissue. Consequently, HMWA may be an important target for the intervention of preventing eclampsia for PIH patients in secondary pregnancy.

LDL fatty acids composition as a risk biomarker of cardiovascular disease

ObjectiveFatty acid composition of Low-density lipoprotein (LDL) particle is an effective factor in LDL oxidation and atherosclerotic plaques formation. This study evaluates the relationship between LDL fatty acid composition and coronary artery disease (CAD). Methods42 men with coronary artery disease (CAD-group) and 40 men without coronary artery disease (non-CAD-group) were selected. LDL fatty acid composition of blood samples was measured by gas chromatography. ResultsOx-LDL was significantly high in CAD-group. Poly unsaturated fatty acids (PUFA) and PUFA/MUFA (Mono unsaturated fatty acids), linoleic acid and arachidonic acid were significantly higher in CAD-group than in non-CAD-group. In CAD-group, a reverse correlation was observed between oleic acid concentrations and ox-LDL levels and a direct correlation was seen between arachidonic acid concentrations and ox-LDL levels. ConclusionComposition of LDL is related to atherosclerosis and CAD. High levels of arachidonic and linoleic acids could increase LDL oxidation and atherosclerotic plaques formation. In addition, LDL arachidonic acid levels could be a better predictor of CAD.

BP.11.07] LDL-OXIDATION, SERUM URIC ACID AND PULSE-WAVE VELOCITY RELATIONSHIP IN CHRONIC KIDNEY DISEASE

Objective: The aim of our study was to evaluate the relationship between oxidized LDL (oxLDL), elevated Serum Uric Acid (SUA) and arterial stiffness in subjects with normal renal function compared with subjects with mild or moderate chronic kidney disease (CKD).Design and method: We selected from the database of the Brisighella Heart Study 205 adult non-smokers subjects, in primary prevention for cardiovascular disease, with normal renal function (M: 99, F: 106), 118 age-matched subjects with mild CKD (M: 55; F: 63) and 94 with moderate CKD (M: 44; F: 50), all visited during the 2012 population survey. All subjects underwent a medical visit including the determination of LDL oxidative susceptibility, oxLDL levels and arterial stiffness parameters such as Augmentation Index (AI) and Pulse Wave Velocity (PWV). Results: PWV was significantly increasing with the degree of CKD (Figure 1). An univariate analysis revealed a direct correlation of PWV with the main anthropometric, haemodynamic and laboratory values usually associated to higher arterial stiffness and a significant inverse correlation with LDL-C lag phase, HDL-C and apoAI (p < 0.05), either in subjects with normal renal function, or with mild or moderate CKD. In a stepwise multiple regression model we observed that in normal renal function and mild CKD groups the main predictors of PWV were age, Systolic Blood Pressure (SBP), ox-LDL, apoB and SUA (p < 0.05), while in moderate CKD group the main predictors were age, SBP and apoB, only (p < 0.05). Conclusions: In our population sample, SUA and oxLDL are significantly related to PWV in subjects with normal renal functions and with mild CKD, but not in subjects with more advanced CKD.