Lipoprotein-associated Phospholipase A2 Concentration Research Articles

Genetic Polymorphism of Lipoprotein-Associated Phospholipase A2 Influences Susceptibility to Gestational Diabetes Mellitus in Chinese Population.

This paper aims to study the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and GDM (gestational diabetes mellitus) by detecting Lp-PLA2 level and its gene polymorphism. From January to June 2022, 82 GDM patients treated in our hospital were included as an experimental group, and 89 healthy pregnant women during the same period were selected as the control group. Lp-PLA2 concentration and TG, TC, HDL-C, and LDL-C levels were tested with specialized instruments in clinical laboratories. The PLA2G7 gene polymorphisms (rs1805017, rs1805018, and rs76863441) were detected by fluorescent probe method and sequencing. Lp-PLA2 concentration was significantly higher in GDM group than control group (P<0.05). Among three polymorphism loci of PLA2G7 gene (rs1805017, rs1805018, and rs76863441) the significant associations were only found in GT genotype of rs76863441 loci (P<0.05). Pregnant women with high levels of Lp-PLA2 concentration are more likely to develop GDM, especially those with PLA2G7 rs76863441 polymorphism. Lp-PLA2 concentration and PLA2G7 rs1805017 polymorphism may be a novel marker for GDM diagnosis and prediction.

Serum lipoprotein-associated phospholipase A2 level is positively correlated with the recurrence risk of acute ischemic cerebral infarction in hypertensive patients

To explore the relationship between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and the risk of acute ischemic stroke (AIS) recurrence in hypertensive patients. This retrospective case-control study was conducted among 211 hypertensive patients with AIS treated in Foshan First People's Hospital, including 35 patients with recurrence of AIS during the 1-year follow-up as confirmed by head CT/MR. In the overall patients, 60 had grade 1 hypertension (including 5 recurrent cases), 76 had grade 2 hypertension (with 11 recurrent cases), and 75 had grade 3 hypertension (with 19 recurrent cases). Univariate analysis, multivariate logistic regression analysis, trend analysis, and smooth curve fitting analysis were performed to explore the correlation between serum Lp-PLA2 level within 24 h after admission and the risk of AIS recurrence. The predictive efficacy of serum Lp-PLA2 level for AIS recurrence in different hypertension grades was evaluated using ROC curve analysis. Serum Lp-PLA2 level, age, NIHSS score at admission, mRS scores at 7 days, homocysteine level and smoking status differed significantly between patients with and without AIS recurrence (P < 0.05). After adjustment for confounding factors, multivariate regression analysis showed that the highest tertile of Lp-PLA2 level was associated with a 4.13-fold increase of AIS recurrence risk compared with the lowest tertile (OR=5.13, 95% CI: 1.35-19.40), and each 1 ng/mL increase of Lp-PLA2 level was associated with a 1% increase of AIS recurrence risk (OR= 1.01, 95% CI: 1.01-1.02). Serum Lp-PLA2 level was shown to positively correlate with AIS recurrence risk, and in patients with grade 3 hypertension, its areas under the ROC curve for predicting AIS recurrence was 0.869 with a specificity of 0.893 and a sensitivity of 0.737. Serum Lp-PLA2 concentration is an independent risk factor and potentially an effective predictor for AIS recurrence in patients with grade 3 hypertension.

Značaj određivanja fosfolipaze A2 udružene sa lipoproteinom kod pacijenata sa antifosfolipidnim sindromom

Introduction: Lipoprotein-associated Phospholipase A2 (Lp-PLA2) is an essential mediator of inflammation, which has a vital role in inflammatory diseases of the vascular system. It has a significant role in the occurrence of thrombosis, the main manifestation of antiphospholipid syndrome. Aim: To investigate the values of Lp-PLA2 in patients with antiphospholipid syndrome (APS) regarding the distribution of all data, age, gender, disease duration, and type of disease. Material and methods: This experimental work analyzed samples of 74 patients diagnosed with APS. Concentrations of Lp-PLA2 were determined by ELISA (Enzyme-Linked Immunosorbent Assay) method. Results: The activity of Lp-PLA2 was higher than the recommended referent values. There is no significant difference in the values of Lp-PLA2 concerning patients' age, gender, disease duration, and type of disease (p &gt; 0,05). There was a statistically significant correlation between the patients' age and the disease duration (rho = 0.359; p = 0.002). Conclusion: Elevated values of Lp-PLA2, so as the correlation between the years of age and duration of APS can be important information to doctors in the appropriate treatment of these patients. It is up to future prospective studies to confirm the significance of Lp-PLA2 determination in patients with APS.

Plasma lipoprotein-associated phospholipase A2 is associated with acute ischemic stroke in patients with atrial fibrillation

ObjectiveTo investigate the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and the incidence of acute ischemic stroke (AIS) in patients with atrial fibrillation (AF). MethodsA total of 257 patients admitted to the Kaifeng Central Hospital were enrolled in this study. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression analysis were used to determine the association between Lp-PLA2 and AIS in patients with AF. ResultsIn AF group, plasma Lp-PLA2 concentrations were significantly higher in patients with AIS than in those without it (277.4 vs 155.1, p < 0.001). And in the group of AIS patients, patients with AF also had a significantly higher level of Lp-PLA2 concentration than those without (277.4 vs 204.2, p < 0.001). The analysis of the ROC curve showed a significant diagnostic value of Lp-PLA2 for the incidence of AIS in patients with AF (AUC = 0.840, 95% CI: 0.737–0.871, p < 0.001), and the optimal cut-off point was 220.5 ng/ml, with a sensitivity and specificity of 82.14% and 75.5%, respectively. All AF patients were divided into two subgroups: the high Lp-PLA2 group (≥220.5 ng/ml) and the low Lp-PLA2 group (<220.5 ng/ml). And multivariate logistic regression analysis showed that after adjustment of confounders, Lp-PLA2 (OR 12.48, 95%CI 5.73–27.16, p < 0.001) was independently associated with the incidence of AIS in patients with AF. ConclusionsPlasma Lp-PLA2 concentration was independently associated with the development of AIS in patients with AF. Lp-PLA2 is a potential biomarker for stratification of risk for AIS in patients with AF.

Serum levels of sLOX-1 and Lp-PLA2 can predict the prognosis of acute cerebral infarction with a high specificity.

Soluble lectin‐like oxidized low‐density lipoprotein receptor‐1 (sLOX‐1) and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) plays an important role in acute cerebral infarction (ACI), whereas its clinical value in predicting the prognosis is unclear. Thus, this study aimed to explore this issue. A total of 127 ACI patients were included in this prospective observational study. The concentrations of sLOX‐1 and Lp‐PLA2 in serum were measured and their relationship with a poor prognosis 90 days after the onset of ACI was analyzed. We found that patients with poor prognosis had higher mean serum levels of sLOX‐1 and Lp‐PLA2. The level of sLOX‐1 and Lp‐PLA2 could predict the functional outcome of ACI. At the optimal cut off value of sLOX‐1 level (1257.92 ng/ml), the sensitivity and specificity for the poor functional outcome were 0.69 and 0.753, respectively, and the area under ROC curve (AUC) was 0.727. Similarly, the optimal value for Lp‐PLA2 level was 160.9 ng/ml, at which the sensitivity and specificity were 0.643 and 0.835, respectively; and the AUC was 0.758. When the two biomarkers were used in combination, the AUC was 0.855, and the sensitivity and specificity were 0.643 and 0.976, respectively, indicating a significant improvement of the diagnostic specificity. The level of sLOX‐1 or Lp‐PLA2 could thus serve as useful biomarkers to predict the functional outcome of ACI. Combined use of both indicators is better than the use of either single indicator, and provides the highest specificity in predicting poor prognosis.

Combined Assessment of Elevated Plasma Lipoprotein-Associated Phospholipase A2 and Plaque Enhancement Improved Accuracy in the Risk of Acute Ischemic Stroke in Patients with Intracranial Artery Stenosis

PurposeWe evaluated the relationship between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and plaque characteristics in patients with intracranial artery stenosis and their clinical relevance in acute ischemic stroke. MethodsEighty-seven patients with intracranial atherosclerotic stenosis (66 males, 21 females) were retrospectively enrolled. Plasma Lp-PLA2 concentration was measured, and vessel wall magnetic resonance imaging (VW-MRI) was used to determine intracranial vascular stenosis and plaque characteristics, including plaque enhancement, surface morphology, and T1 hyperintensity. Binary logistic regression was used to evaluate the relationship between Lp-PLA2 concentration and plaque characteristics of intracranial artery after adjusting for demographic and confounding factors and to assess their diagnostic efficacy for the risk of acute ischemic stroke. ResultsAfter adjustment for demographic, medication and related lipid factors, Lp-PLA2 elevation was associated with plaque enhancement (odds ratio [OR]=12.7, 95% confidence interval [CI] 2.51–64.82, P=0.002) and surface irregularity (OR=2.9, 95% CI 1.06–7.98, P=0.038). Both Lp-PLA2 elevation (OR=8.8, 95% CI 1.64–47.72, P=0.011) and plaque enhancement (OR=34.3, 95% CI 5.88–200.4, P=0.001) were associated with acute ischemic stroke. Receiver operating characteristic curve analysis showed that the area under the curve for Lp-PLA2 concentration and plaque enhancement combined in the diagnosis of acute ischemic stroke was 0.884, significantly higher than that for Lp-PLA2 concentration (0.724) and plaque enhancement (0.794) alone. ConclusionElevated Lp-PLA2 is associated with plaque enhancement and plaque surface irregularity. Combined assessment of Lp-PLA2 concentration and plaque enhancement is of greater diagnostic value for the risk of acute ischemic stroke in patients with intracranial artery stenosis.

The prognostic value of the serum inflammatory biomarkers in patients with carotid atherosclerosis

20 % of ischemic stroke appear to originate from carotid artery atherosclerotic disease. Serum biomarkers reflecting the activity of atherosclerotic process and may help for estimate risk of acute cerebrovascular events. Several serum inflammatory markers have been proposed for risk assessment, but their prognostic role less known.&#x0D; The aim of this study is to clarify the prognostic value of biomarkers of atherosclerosis lipoprotein-associated phospholipase A2 (Lp-PLA2) and E-selectin in patients with symptomatic and asymptomatic carotid stenosis.&#x0D; Materials and methods. The study involved 106 patients with atherosclerotic carotid stenosis &gt;50 % (74 men and 32 women, mean age 62.6±0.9) from which 76 symptomatic (35 with acute ipsilateral atherothrombotic stroke and 41 after carotid endarterectomy) and 30 asymptomatic patients. The control group consisted of age- and sex-matched 20 healthy subjects. The level of serum Lp-PLA2 and E-selectin was determined using a commercially available enzyme-linked immunosorbent assay kit.&#x0D; Results. The level of Lp-PLA 2 was in general significantly higher (p&lt;0.05) in patients groups than in the control group and most high Lp-PLA2 concentration was in groups of symptomatic patients who underwent carotid endarterectomy. The level of E-selectin in the study patients was significantly higher than in the control group (p&lt;0.05). The correlation of Lp-PLA 2 with E-selectin was significant for total patients (R=0.365664, p=0.00085) and group after carotid endarterectomy (R=0.429143, p=0.01796), but not for asymptomatic group (p&gt;0.05). Receiver Operating Characteristics curves of logistic regression models which takes into joint both indicators was specificity and sensitive for predicting the occurrence of ischemic stroke.&#x0D; Conclusion. Conducted study show that the levels of Lp-PLA 2 and E-selectin have a significant impact on the development of stroke in patients with atherosclerotic carotid stenosis and can be used to predict it. A multidimensional model of the dependence of the probability of stroke on a linear combination of Lp-PLA 2 and E-selectin allows to obtaining significantly higher characteristics of the accuracy of stroke prediction than models with each factor alone.

Lp-PLA2, a potential protector of lung cancer patients complicated with pleural effusion from lung diseases, proves effective for the diagnosis and pathological classification of lung cancer

Abnormal lipid metabolism plays a crucial role in cancers, but few studies have investigated the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and lung cancer. In this study, 58 benign lung disease (LB) and 57 lung cancer (LC) patients complicated with pleural effusion (PE) were included, and their fasting serum and PE samples were collected. Results showed that serum Lp-PLA2 in the LC group was lower than that in the LB group, and other serum lipids were higher (P < 0.05). Tumor markers from serum and the PE samples of LC patients were higher than those in the LB group (P < 0.05). Serum prealbumin (PA) in LC patients was higher than that in the LB group, and serum C-reactive protein (CRP) and procalcitonin (PCT) were lower (P < 0.05). In the LC group, serum Lp-PLA2 concentration was positively correlated with serum triglyceride (TG), Lp (a), carbohydrate antigen 199 (CA199), nutritional markers, and Lp-PLA2 in PE and negatively correlated with serum high-density lipoprotein cholesterol (HDLC), Apolipoprotein A1 (APOA1), CRP, PCT, and alpha fetoprotein (AFP) and LDH in PE. The ROC curve showed that the cutoff level of serum Lp-PLA2 for diagnosing LC was 226.685 (U/L) (sensitivity: 0.632, specificity: 0.793), while the C-index of the nomogram model combined with serum Lp-PLA2, age, and gender was 0.750. In LC patients, the higher serum Lp-PLA2 indicated higher probability of adenocarcinoma and lower probability of squamous cell carcinoma (SCC). In conclusion, Lp-PLA2 may be a protective factor of lung cancer among lung disease patients complicated with pleural effusion, and it would facilitate the diagnosis and pathological classification of lung cancer.

Relationship between Plasma Lipoprotein-Associated Phospholipase A2 Concentrations and Apolipoprotein in Stable Coronary Artery Disease Patients

Background Increasing evidence states that the plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and apolipoprotein particles are regarded as the risk maker for cardiovascular heart disease. Nevertheless, the issue about whether Lp-PLA2 is associated with apolipoprotein particles in individuals who have been diagnosed as stable coronary artery disease (CAD) remains largely unexplored. Method All 569 participants engaged in this research, who never took lipid-lowering drugs, had been divided into groups by the coronary angiography (CAG), namely, stable CAD: n = 291; non-CAD: n = 278. The results concerning Lp-PLA2 levels were calculated by Elisa Kit, while apolipoprotein particles were measured by the department of laboratory. Results The plasma concentration of Lp-PLA2 was remarkably higher in stable CAD group than the non-CAD group (136.0 ± 60.5 ng/mL vs. 113.2 ± 65.6 ng/mL, P < 0.001). Pearson correlation analyses explained the plasma Lp-PLA2 concentration was correlated with apoB (r = 0.390, P < 0.001) and apoB/apoA1 (r = 0.450, P < 0.001), not associated with apoA1 (r = −0.099, P = 0.101). Conversely, the association remains unobserved among non-CAD patients except apoA1. Moreover, multiple linear regression revealed the relations between Lp-PLA2 concentrations and apoB (β = 0.390, P < 0.001), as well as apoB/apoA1 (β = 0.450, P < 0.001), but not apoA1 (β = −0.099, P = 0.121). After adjustment for several risk factors regarding CAD, like hypertension, gender, smoking, age, and diabetes mellitus, there had still been positive associations between the Lp-PLA2 concentration and apoB (β = 0.364, P < 0.001), as well as apoB/apoA1 (β = 0.390, P < 0.001). Conclusion The plasma levels of Lp-PLA2 provide positively a key link with apoB, apoB/apoA-1 among stable CAD, denoting the communication between Lp-PLA2 and apolipoprotein particles in the state of CAD.

Role of markers of inflammation and endothelial dysfunction in the prognosis of the development of cardiovascular complications in patients with coronary artery disease and metabolic syndrome after coronary stenting

Aim To study the role of inflammation markers and endothelial dysfunction in predicting the risk of cardiovascular event following a percutaneous coronary intervention (PCI) in patients with ischemic heart disease (IHD) and metabolic syndrome (MS).Materials and methods 80 patients (72 men; median age, 56 (50;63) years) with IHD and PCI were evaluated. Based on the presence of MS according to NCEP-ATP III criteria, patients were divided into two groups, group 1 without MS (n=32) and group 2 with MS (n=48). The control age- and sex-matched group included 15 people without cardiovascular diseases. Serum concentrations of tumor necrosis factor α (TNFα), interleukin 6 (IL-6), IL-10, lipoprotein-associated phospholipase A2 (LP-PLA2), and endothelin 1 were measured by enzyme-linked immunosorbent assay (ELISA). Patients were followed up for 12 months after PCI with evaluation of the incidence of adverse cardiovascular events. Statistical analysis was performed with Statistica 10.0 and Medcalc 19.2.6 software. Differences between variables were considered statistically significant at р&lt;0.05. Potential predictors were determined by the ROC analysis with construction of ROC curves, calculation of AUC (area under the curve), identification of COP (cut-off point by the Youden's index), and sensitivity (Se) and specificity corresponding to the COP.Results Patients with MS had statistically significantly higher serum levels of inflammatory markers than patients of the control group. Concentration of the intravascular inflammation marker, PL-PLA2, was 2.7 times higher in group 1 and 5.1 times higher in group 2 than in the control group (р&lt;0.001). Concentrations of endothelin 1 were 1.9 times higher in group 1 and 3.7 times higher in the MS group compared to the control. At one year after PCI, the incidence of adverse outcomes in the form of cardiovascular events was higher for patients with MS: 10 (20.8 %) cases of stent restenosis and 13 (27.1 %) episodes of coronary atherosclerosis progression according to results of repeated coronarography vs. 2 (6.3%) restenosis cases (χ2-10.853; р=0.002) and 2 (6.3%) episodes of atherosclerosis progression (χ2-23.651; р=0.001) for patients without MS. The groups did not differ in rates of myocardial infarction and cardiac death. The most significant predictors of unfavorable prognosis were LP-PLA2 concentration &gt;983.83 ng/ml (area under the ROC curve, 0.867; sensitivity, 80 %; specificity, 100%; р&lt;0.001) and endothelin 1 overexpression &gt;0.852 fmol/ml (area under the ROC curve, 0.885; sensitivity, 85.5 %; specificity, 83.6 %; р&lt;0.001).Conclusion Patients with MS were characterized by more pronounced imbalance of pro- and anti-inflammatory factors. Concentrations of LP-PLA2 &gt;983.83 ng/ml and endothelin 1 &gt;0.852 fmol/ml were shown to be predictors of unfavorable prognosis for patients with IHD and MS after PCI with coronary stenting.

Photoelectrochemical immunoassay of lipoprotein-associated phospholipase A2 via plasmon-enhanced energy transfer between gold nanoparticles and CdS QDs/g-C3N4.

A facile and feasible photoelectrochemical (PEC) immunoassay based on plasmon-enhanced energy transfer between gold nanoparticles (AuNPs) and CdS quantum dots (QDs)/g-C3N4 nanosheets was developed for the ultrasensitive detection of lipoprotein-associated phospholipase A2 (Lp-PLA2). To construct such a sensing platform, the immunosensor was prepared by immobilizing Lp-PLA2 on a CdS QDs/g-C3N4-modified electrode. A competitive-type immunoreaction was utilized for Lp-PLA2 detection, with AuNP-labeled anti-Lp-PLA2 antibody used as the competitor. Introducing AuNPs with the specific antibody for the antigen target Lp-PLA2 led to heavy quenching of the photocurrent of CdS QDs/g-C3N4 due to the plasmon-enhanced energy transfer between AuNPs and CdS QDs. The quenching efficiency decreased with increasing target Lp-PLA2 concentration. Under optimal conditions, the PEC immunosensor presented a good photocurrent response to the target Lp-PLA2 in the dynamic linear range of 0.01-300ngmL-1, with a low detection limit of 5.3pgmL-1. Other biomarkers and natural enzymes did not interfere with response of this system. The reproducibility and accuracy of this method for the analysis of human serum specimens were evaluated, and the results given by the method developed here were found to closely correspond to the results obtained with commercial Lp-PLA2 ELISA kits. Importantly, this protocol offers promise for the development of exciton-plasmon interaction-based PEC detection systems. Graphical abstract ᅟ.

Exploration of serum sensitive biomarkers of fatty liver in dairy cows

Serum proteins are sensitive with diseases in dairy cows, and some of them could be used as biomarkers for fatty liver. This study aimed to explore serum biomarkers for fatty liver in dairy cows. A total of 28 early lactating dairy cows were chosen from a commercial dairy herds, liver samples were collected for determining concentration of triacylglycerol (TAG), and serum samples were collected for measuring fibroblast growth factor-21 (FGF-21), adiponectin, Lipoprotein-associated phospholipase A2 (LP-PLA2), and hemoglobin (Hb). Dairy cows were divided into fatty liver (liver TAG > 5%, wet weight) and control group (liver TAG < 5%, wet weight). Concentration of FGF-21 was greater in fatty liver cows, while the concentration of LP-PLA2 and Hb was less. The concentration of FGF-21 and total Hb had strong correlation with the liver TAG as well as good prediction power (kappa value = 0.79 and 0.58, respectively). These results suggested that the serum concentration of FGF-21 and total Hb could be potentially used as fatty liver biomarkers in lactating dairy cows.

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by combined RNA interference of lipoprotein-associated phospholipase A2 and YKL-40.

To test the hypothesis that combined RNA interference (RNAi) of lipoprotein-associated phospholipase A2 (Lp-PLA2) and YKL-40 is superior to RNAi of Lp-PLA2 or YKL-40 alone in ameliorating atherosclerosis. A total of 120 apolipoprotein E-deficient mice (apoE-/- mice) were randomly divided into five groups, including the vehicle alone, scrambled RNAi, Lp-PLA2 RNAi, YKL-40 RNAi, and combined Lp-PLA2 and YKL-40 RNAi groups. Constrictive collars were used to induce plaque formation. Lp-PLA2 RNAi and YKL-40 RNAi viral suspensions were transduced into carotid plaques of the mice. Carotid plaques were harvested for histological analysis four weeks after viral vector transduction. Inflammatory gene expression in the plasma and atherosclerotic plaques was determined by ELISA and real-time PCR. Four weeks after RNAi, the serum concentration and plaque mRNA expression of Lp-PLA2 and YKL-40 were remarkably attenuated, leading to reduced inflammatory gene expression. Plaques from the Lp-PLA2 or YKL-40 RNAi group showed lower lipid content, higher collagen content, increased fibrous cap thickness, and lower mRNA expressions of MCP-1 and MMP-8 than than those in the vehicle and scramble groups. When compared with the isolated Lp-PLA2 or YKL-40 RNAi group, the combined Lp-PLA2 and YKL-40 RNAi group exhibited higher collagen content and fibrous cap thickness, and lower lipid content and local inflammation. The beneficial effects of RNAi were independent of the plasma lipoprotein profile. Combined RNAi of Lp-PLA2 and YKL-40 is superior to RNAi of Lp-PLA2 or YKL-40 alone in ameliorating atherosclerosis.

Association of statin therapy with plasma fatty acids profile and lipoprotein-associated phospholipase A2 concentration

Association of statin therapy with plasma fatty acids profile and lipoprotein-associated phospholipase A2 concentration

Association of Lipoprotein-Associated Phospholipase A2 with the Prevalence of Nonalcoholic Fatty Liver Disease: A Result from the APAC Study

Nonalcoholic fatty liver disease (NAFLD) is a worldwide chronic liver disease. Few studies have investigated the association between NAFLD and Lipoprotein-associated phospholipase A2 (Lp-PLA2), a unique enzyme correlated with oxidative stress. The aim of this study was to assess the relationship between Lp-PLA2 and NAFLD in a Chinese community-based cohort. A total of 1587 adults aged ≥40 years were enrolled in the current study. Participants underwent a standardized evaluation. The serum Lp-PLA2 concentration was measured by ELISA and NAFLD was diagnosed by ultrasonography. Multivariable logistic regression was used to assess the association between Lp-PLA2 and NAFLD. Increased Lp-PLA2 levels were significantly associated with decreased NAFLD prevalence after adjusting for other potential confounders. The adjusted ORs of NAFLD in Q2, Q3 and Q4 compared with Q1 were 0.88 (0.64–1.21), 0.71 (0.51–0.98) and 0.67 (0.48–0.95), respectively (P < 0.05). Furthermore, the adjusted ORs of moderate and heavy NAFLD in Q2, Q3 and Q4 compared to Q1 were 0.64 (0.41–1.01), 0.48 (0.29–0.80) and 0.47 (0.28–0.79), respectively (P < 0.01). In conclusions, increased Lp-PLA2 levels were independently associated with decreased NAFLD prevalence.

Myeloperoxidase level and inflammatory markers and lipid and lipoprotein parameters in stable coronary artery disease

BackgroundMyeloperoxidase (MPO) impairing endothelial functions. We investigated whether increasing concentration of myeloperoxidase (MPO) and inflammatory markers induce progression and incident acute coronary syndrome (ACS) in stable coronary artery disease (SCAD) patients. Therefore, the concentration of MPO, lipids, lipoproteins (apo(apolipoprotein) AI, apoB, lipoprotein associated phospholipase A2 (LpPLA2) level), inflammatory markers (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) concentration) were examined.MethodsThis study concerned 67 SCAD patients divided into groups: all patients, patients with MPO < 200 ng/ml, MPO 200–300 ng/ml, MPO > 300 ng/ml concentration and 15 controls. ApoAI, apoB and hsCRP levels were examined using the immunonephelometric method, and MPO, LpPLA2, IL-6, TNF-α concentration was performed by using Quantikine ELISA kit R&D Systems.ResultsIn the all patients, and in group with MPO 200–300 ng/ml TC, LDL-C, nonHDL-C, LpPLA2 concentration and TC/HDL-C, LDL-C/HDL-C ratios were insignificant, and significantly higher concentration of TG, apoB, MPO, inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios but HDL-C, apoAI level and HDL-C/apoAI ratio were significantly reduced. In the group of patients with MPO < 200 ng/ml, level of TC, LDL-C, nonHDL-C, apoAI, apoAII, LpPLA2 and MPO and LDL-C/HDL-C ratio were in-significant, HDL-C was decreased but apoB, TG, inflammatory markers, apoB/apoAI, TG/HDL-C, MPO/apoAI, MPO/HDL-C ratio were significantly increased. In the group of patients with MPO > 300 ng/ml concentration of TC, LDL-C, nonHDL-C, apoAII, LpPLA2 and LDL-C/HDL-C ratios were not significant, but HDL-C and apoAI concentrations were significantly decreased. The concentrations of TG, apoB, MPO and inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios were significantly increased compared to the controls. The apoAI concentration was significantly decreased and the concentration of MPO and hsCRP as well as MPO/apoAI and MPO/HDL-C ratios were significantly higher as compared to the group of patients with MPO < 200 ng/ml.Spearman’s correlation test showed a positive correlation between MPO concentration and MPO/apoAI and MPO/HDL-C ratios in all patients and MPO < 200 ng/ml, MPO 200–300 ng/ml. The patients with MPO > 300 ng/ml showed a positive correlation between the concentration of MPO and the level of hsCRP and IL-6, and a negative correlation between MPO/apoAI ratio and the concentration of HDL-C, apoAI and apoAII.ConclusionThe results suggest that moderate dyslipidemia and dyslipoproteinemia deepening of inflammation, and inflammation slowly induce increase MPO concentration which decrease apoAI and HDL-C level and disturb HDLs function. The increasing MPO level and MPO/HDL-C, MPO/apoAI ratios can differentiate the SCAD patients at the risk of acute coronary syndrome (ACAD) and stroke.

Cerebral atherosclerosis: a biomarker profile

To assess the changes in several biomarkers in patients with atherosclerosis of brachiocephalic arteries and shape a biomarker profile of cerebral atherosclerosis as an integrative index. The study included 124 patients with atherosclerotic lesions of internal carotid arteries (82 men and 42 women) aged from 37 to 73 years. The patients were stratified by history of prior stroke into 'asymptomatic' and 'symptomatic'. Along with general clinical and neurological examinations, ultrasound analysis of brachiocephalic arteries, neuroimaging, identification of biomarkers reflecting different stages of atherogenesis and evaluation of pathomorphological parameters of atherosclerotic plaques removed during carotid endarterectomy surgery were performed. Concentrations of NO2, NO3 and NO in blood plasma significantly differed between groups: 58.4, 43.3 and 15 mcmol/l, respectively, in the symptomatic group and 45, 19.2 and 25.8 mcmol/l in the asymptomatic group. The pro-inflammatory character of changes in atherosclerosis was confirmed by the increase in the concentration of lipoprotein-associated phospholipase A2 in patients with stroke (354.72±44.16 ng/ml versus 298.45±54.12 ng/ml). The level of the atheroprotective marker adiponectin decreased significantly in 'symptomatic' patients. Significant changes towards the prothrombotic state of blood were identified via levels of blood markers of fibrinolytic activity: plasminogen tissue activator and plasminogen activator inhibitor-1. Together with other diagnostic methods, identification of biomarkers can increase the accuracy of prognosis and prevention of sudden cardiovascular death. The authors have developed a scale of biomarker 'burdeness' of the patient with cerebral atherosclerosis that may be a first step to individualized prevention of associated ischemic complications.

The role of Lp-PLA2 and biochemistry parameters as potential biomarkers of coronary artery disease in Asian South-Indians: a case-control study.

Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Lipoprotein associated phospholipase A2 (Lp-PLA2) is an emerging biomarker for inflammation that has shown association with CAD. Its significance in the Asian Indian population is not clearly known. We sought to compare the possible association of various biomarkers of atherosclerosis along with Lp-PLA2, in symptomatic individuals with CAD vs. healthy controls in Asian South-Indians. We conducted a cross-sectional case control study at three centers in a South Indian population. A total of 100 CAD patients with acute coronary syndrome (ACS), 100 age and gender matched healthy controls participated, of which, 166 subjects or 83 case-control pairs with complete data for both participants were identified for the statistical analysis. Lp-PLA2 concentration and activity were measured using PLAC test and PLAC activity assay respectively (diaDexus Inc., San Francisco, CA, USA), while all other parameters were measured using standard commercially available kits. We enrolled a total of 200 subjects (mean age 50.7±9.6 years, 87.5% males). A total of 83 subjects completed the study in the CAD group (mean age 51 ±8.9 years, 85% males) and 83 subjects in the control group (mean age 50±8.9 years, 86.5% males). In the CAD group, Lp-PLA2 concentration positively correlated with TC (ρ=0.19, P=0.02), non-HDL-C (ρ=0.20, P=0.02), Lp-PLA2 activity (ρ=0.27, P=0.001) and Lp(a) (r=0.25, P=0.02). Lp-PLA2 activity correlated positively with TC (ρ=0.28, P=0.001), LDL-C (ρ=0.30, P<0.001), non-HDL-C (ρ=0.35, P<0.001), ApoB (ρ=0.35, P<0.001) and negatively correlated to HDL-C (ρ=-0.24, P=0.004). Cox proportionality hazards model revealed Lp-PLA2 concentration (β=0.006, SE =0.002, P=0.009) to have positive association with the event of CAD, while negative association was observed for ApoA1 (β=-0.06, SE =0.02, P=0.001). ROC analysis revealed that the highest quartile of Lp-PLA2 concentration to have area under curve (AUC) of 0.80 (95% CI, 0.65-0.9; P<0.001) with cut off value of >427 ng/mL and ApoA1 with AUC of 0.78 (95% CI, 0.70-0.85; P<0.001) with cut off value of ≤129.6 mg/dL with the optimum balance of sensitivity and specificity. In this study population, circulating plasma Lp-PLA2 was found to be elevated in CAD group. ApoA1 showed negative association and Lp-PLA2 concentration showed positive association with risk for CAD. In the highest quartile, Lp-PLA2 concentration had the best diagnostic utility. Our results support the hypothesis that Lp-PLA2 may be a potential risk marker for CAD in Asian Indians.

HUCMNCs protect vascular endothelium and prevent ISR after endovascular interventional therapy for vascular diseases in T2DM rabbits.

The therapeutic effect of transplantation of human umbilical cord blood cell-derived mononuclear cells (HUCMNCs) on treating in-stent restenosis (ISR) after endovascular interventional therapy (EIT) was evaluated in preclinical rabbit model of type 2 diabetes mellitus (T2DM)-related peripheral artery disease (PAD). HUCMNCs were transplanted to T2DM rabbits subjected to femoral artery occlusion surgery and received EIT. Serum concentration of soluble vascular endothelial cadherin (VE-cad) and plasma concentration of lipoprotein-associated phospholipase A2 (Lp-PLA2) were determined with enzyme-linked immunosorbent assay before and after the transplantation. The injury and the recovery of right femoral artery at stenting site were evaluated with Hematoxylin and Eosin (HE) staining. HUCMNCs purified from umbilical cord blood were 100% CD45+ and 96.5% CD34- with round or oval morphology and adherent growth pattern. The soluble VE-cad and Lp-PLA2 were significantly attenuated after HUCMNC transplantation. The intimal area and the ratio between intimal area and medium film area in the dilated occlusion site were also dramatically decreased 4weeks after receiving HUCMNCs. HUCMNC transplantation is effective in protecting vascular endothelial function and preventing ISR after EIT in T2DM rabbits suffering from PAD.

AMP-activated protein kinase mediates the effects of lipoprotein-associated phospholipase A2 on endothelial dysfunction in atherosclerosis.

The present study aimed to investigate the effects of lipoprotein-associated phospholipase A2 (Lp-PLA2) on endothelial dysfunction in an in vitro cell model of atherosclerosis, and to determine whether AMP-activated protein kinase (AMPK) mediates the effects of Lp-PLA2 on endothelial dysfunction. A total of 392 patients with coronary artery disease (CAD), including various sub-conditions, were recruited, and the plasma concentrations of Lp-PLA2 were evaluated. In addition, an in vitro model of atherosclerosis was established by exposing human umbilical vein endothelial cells (HUVECs) to oxidized low-density lipoprotein (oxLDL). SB-435495 was used to inhibit Lp-PLA2, and compound C was used to suppress AMPK expression. Lp-PLA2, AMPKα and phosphorylated-AMPKα (T172) expression in HUVECs were evaluated using western blot analysis. The concentrations of nitric oxide (NO), endothelin 1 (ET-1), intercellular adhesion molecule 1 (ICAM-1) and platelet/endothelial cell adhesion molecule 1 (PECAM-1) in cell culture supernatant were determined using commercially available ELISA kits. MTT assays were employed to indicate changes in cell viability. The current study found the plasma Lp-PLA2 levels were elevated in the CAD patients with stable angina pectoris, unstable angina pectoris, acute coronary syndromes and acute myocardial infarction, compared with a healthy control population. In addition, the in vitro results showed that Lp-PLA2 expression levels were elevated in oxLDL-exposed HUVECs. Lp-PLA2 suppression could increase cell viability, induce the production of NO and decrease the secretion of ET-1, in addition to suppressing the expression of cell adhesion molecules, including ICAM-1 and PECAM-1 in oxLDL-exposed HUVECs. The expression of AMPKα and phosphorylated-AMPKα (T172) was regulated by Lp-PLA2, and AMPK suppression was able to reverse the effects of Lp-PLA2 with regard to cell viability, endothelial vasorelaxation capacity and the secretion of adhesion molecules in oxLDL-exposed HUVECs. In conclusion, the present study provides initial evidence that Lp-PLA2 is able to cause endothelial dysfunction in an in vitro model of atherosclerosis, and the effects of Lp-PLA2 on endothelial dysfunction was at least partially a result of the downregulation of AMPKα, thus contributing to the progression of atherosclerosis.