Lp-PLA2 Levels Research Articles

Role of vitamin D in risk factors of patients with type 2 diabetes mellitus

Introduction and objectivesPrevious observational studies have suggested that low vitamin D status is associated with high circulating C-reactive protein levels, as well as other plasma inflammatory cytokines. However, there is no study to explore the relationship between vitamin D status and Lp-PLA2, a new biomarker of vascular-specific inflammation. The aim of this study was to examine the association between vitamin D status and circulating Lp-PLA2 levels in subjects with type 2 diabetes mellitus. Material and methodsThis descriptive cross-sectional study enrolled diabetic subjects who underwent physical examination at Taizhou People's Hospital between August 2016 and January 2017. Blood pressure, anthropometry, metabolic profiles, serum 25(OH)D levels and Lp-PLA2 mass levels were measured in all participants. ResultsA total of 196 participants were recruited into this study. The vitamin D insufficiency group had higher serum LP-PLA2 levels than the vitamin D sufficiency group (t=−2.765, p=.005). A significant negative correlation was noted between Lp-PLA2 and 25(OH)D in the vitamin D insufficiency group (r=−0.364, p=0.009). However, no significant relationship between serum Lp-PLA2 concentration and 25(OH)D levels was observed in subjects with vitamin D sufficiency. ConclusionsFrom this cohort of patients with type 2 diabetes, regardless of traditional cardiovascular risk factors, we observed a statistically significant inverse relation between Lp-PLA2 and 25(OH)D at levels <30ng/mL.

Evaluation of Serum Levels of LP-PLA2 and CA-242 in Adult Male Cigarette Smokers in Nnewi Metropolis

Background: Cigarette smoking is a behavioural lifestyle in which a substance is burned and the resulting smoke breathed into the body system. Thus, cigarette smoking is a known public health challenge given the number of tobacco-related diseases like hypertension, lung cancer, cardiovascular diseases (CVD) etc. leading to increased mortality in developed and developing countries. Notwithstanding that the effects of smoking are well documented, individuals who practice cigarette smoking are still on the increase most especially in the developing countries. Study Design/Aim: This was a cross-sectional study designed to evaluate the serum levels of Cancer Antigen-242 (CA-242) and Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) in adult male smokers in Nnewi Metropolis, as emerging inflammatory biomarkers. Materials and methods: A total of 135 subjects aged between 16-65 years were selected for this study. They were classified into 2 major groups (test and control); comprising of 85 cigarette smokers (55 and 30 as test subjects for the evaluation of CA-242 and Lp-PLA2) respectively and 50 non-cigarette smokers (35 and 15 as control subjects for CA-242 and Lp-PLA2 evaluations) respectively. A well-structured questionnaire was used for the collation of information from the participants. Results: the mean serum level of Lp-PLA2 was significantly elevated (P&lt;0.05) in cigarette smokers (67.52±27.29) compared with the non-smokers (63.63±20.81). While the serum level of CA-242 among smokers (1.77±0.70) was of no significant difference (P=0.711) when compared with the non-smokers (1.81±0.20). More so, the mean serum levels of Lp-PLA2 correlated positively with the duration of smoking (r=0.297) and age (r=0.085) in male cigarette smokers. However, there were negative relationships when CA-242 were correlated with duration of smoking (r = -0.156) and age of smokers (r=-0.155). Conclusion: The increased level of Lp-PLA2 along with its positive correlation with other traditional markers like age and smoking duration suggests that Lp-PLA2 is a suitable biomarker to predict cardiac related diseases among cigarette smokers. This is because, Lp-PLA2 is a more specific cardiac predictor compared to the non-specific conventional biomarkers. We therefore suggest that Lp-PLA2 as an independent advanced predictor of cardiovascular disease be further evaluated using follow-up studies with better sample size in CVDs related cases

Effects of Cervical Rotatory Manipulation (CRM) on Carotid Atherosclerosis Plaque in Vulnerability: A Histological and Immunohistochemical Study Using Animal Model.

Background The safety of cervical rotatory manipulation (CRM) is still controversial, especially in patients with carotid artery atherosclerosis (CAS). The study aimed to investigate the effects of CRM on carotid plaques in vulnerability. Methods 50 rabbits were randomly divided into four groups: model rabbits with CRM [CAS-CRM (n=15)]; model rabbits without CRM [CAS (n=15)]; normal rabbits with CRM [Normal-CRM (n=10)]; and Blank-control group (n=10). CAS disease models were induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. Then, CRM technique was performed in CAS-CRM and Normal-CRM groups for 3 weeks. In the end, determination of serum level of hs-CRP and Lp-PLA2, histological analysis under HE and Masson trichromic staining, and immunohistochemical analysis with CD34 and CD68 antibody were completed in order. Results Carotid stenosis rates on successful model rabbits ranged from 70% to 98%. The CAS-CRM group had an increased level of hs-CRP (P<0.05), in comparison with the CAS group, whereas effects were not significant between the Normal-CRM group and Blank-control group. In comparison with the CAS group, the positive expression of CD34 and CD68 in the CAS-CRM group increased significantly (P<0.05). Conclusion CRM therapy may increase the vulnerability of carotid plaque in rabbits with severe CAS.

937. Virally Suppressed PLH Switching From Abacavir to Tenofovir Alafenamide Did Not Have Changes in Immune Activation or Inflammation

BackgroundAbacavir (ABC) use has been associated with increased risk of myocardial infarction in persons living with HIV (PLH). Its mechanism is unknown, but may involve immune activation inflammation, and/or altered platelet reactivity. In the current analysis, we compared changes in biomarkers of immune activation and inflammation associated with increased cardiovascular (CV) mortality in virally suppressed PLH who switched off ABC to tenofovir alafenamide (TAF) to those who remained on ABC.MethodsIn a randomized, double-blinded, active-controlled trial (GS US 311–1717), virally suppressed PLH on a stable regimen containing ABC plus lamivudine (3TC) were randomly assigned (1:1) to maintain therapy or to switch to TAF plus emtricitabine (FTC) while continuing their third agent. At baseline (BL) and weeks 4, 12, 24, and 48 plasma markers (IL-6, hsCRP, D-Dimer, sCD14, sCD163, TNF-R1, and TNF-R2) were measured by ELISA; Lp-PLA2 levels were measured by the Plac assay. Differences between treatment groups overtime were assessed by 2-sided Wilcoxon rank-sum tests.ResultsOf 556 PLH randomized, 548 had samples available for biomarker assessments (TAF: 274; ABC: 274), both arms were of similar CD4 (median 671 cells/μL), age (median 52 years), race (73% white), but there were fewer women in the TAF arm (14% vs. 22%, P = 0.015) at baseline (BL). Mean BL ASCVD scores were 7.9 in both arms (>7.5 is increased CV risk). BL biomarker concentrations were similar between arms: most had high concentrations of Lp-PLA2 ≥200 ng/mL (94%) and one-third had elevated hsCRP levels >3 mg/L (34%). After switching from ABC to TAF, sCD14 had an early (W12) decreased (−3.4% vs. −0.1%, P = 0.023), while sCD163 increased at both W4 (2.5% vs. −1.2%, P = 0.02) and W24 (1.4% vs. −0.8%, P = 0.025) in the TAF arm; levels of sTNF-R1 also increased through W24 (3.2% vs. 0.2%, P = 0.003) (figure). There were no significant differences in percentage changes from BL between arms for levels of Lp-PLA2, hsCRP, IL-6, D-dimer, or TNF-R2.ConclusionPrior to switching from ABC to TAF, virally suppressed PLH with mean ASCVD scores of 7.9 had elevated levels of CV risk markers (Lp-PLA2 and hsCRP). Switching off ABC to TAF was not associated with any meaningful change in markers of immune activation or inflammation, suggesting that the ABC-associated increased MI risk may involve an alternative etiology. Disclosures G. Mccomsey, Merck: Consultant, Consulting fee. ViiV: Consultant, Consulting fee. Gilead: Consultant, Consulting fee. Astellas: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. P. Mallon, Gilead Sciences: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Grant recipient and Speaker honorarium. GSK Ireland: Grant Investigator and Scientific Advisor, Grant recipient. A. Winston, Gilead, ViiV Healthcare, BMS, Janssen and Merck: Consultant, Grant Investigator, Investigator and Speaker’s Bureau, Educational grant, Grant recipient, Research grant and Speaker honorarium. D. Sengupta, Gilead Sciences: Employee and Shareholder, Salary and Stock. M. Yan, Gilead Sciences: Employee and Shareholder, Salary and Stock. M. S. Rhee, Gilead Sciences: Employee and Shareholder, Salary and Stock. M. Das, Gilead Sciences: Employee and Shareholder, Salary and Stock.

The Therapeutic Efficacy of Danhong Injection Combined With Percutaneous Coronary Intervention in Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Background: Percutaneous coronary intervention (PCI) is widely used in treatment of acute coronary syndrome (ACS) clinically. It is believed that Danhong injection (DHI) extracted from salviae miltiorrhizae and flos carthami combined with PCI could increase the therapeutic efficacy on ACS. We provide an updated meta-analysis with detailed information on combination of DHI and PCI therapy.Materials and Methods: Electronic databases were searched for appropriate articles without language limitations on key words before October 22, 2017. All trails were screened according to certain criteria. Quality of eligible studies was also assessed. We made a detailed record of outcome measurements. RevMan 5.3 software was used to perform the meta-analysis.Results: 14 articles involving 1533 patients with ACS were selected. Compared to PCI treatment alone, total efficacy rate (TER) was enhanced and major adverse cardiovascular events (MACE) were reduced significantly for the combination of DHI and PCI (P < 0.00001). Vascular endothelial function was improved by significantly decreasing the contents of ET-1, vWF and increasing the levels of NO and FMD (P < 0.00001). The serum levels of IL-1, IL-6, IL-18, TNF-α, LpPLA2, MMP-9, and pentraxin-3 were significantly decreased (P < 0.00001), whereas IL-10 in serum was increased (P < 0.00001), indicating a stronger anti-inflammatory effect of the combination. The combination therapy decreased the serum levels of CD62P, PAGT, PADT, FIB-C significantly (P < 0.05), which was beneficial for preventing coagulation of platelets. Blood lipid was also affected by regulating TC, TG, LDL, and HDL, but the results were not statistically significant (P > 0.05). Cardiac function was improved by increasing LEVF (P = 0.006) but not LVED (P = 0.08). The combination treatment was associated with an improvement in antioxidant effect by decreasing MDA and increasing SOD significantly (P < 0.00001).Conclusion: Combination of DHI and PCI in treatment of ACS could improve TER and reduce incidence of MACE after PCI therapy. These effects may be mediated by combined actions of several mechanisms. However, these results of this study should be handled cautiously due to the limitations of this research. Several rigorous RCTs are in need to confirm these findings.

Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Aims/hypothesisLipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2. A final aim was to evaluate the effect of cholesterol on cellular Lp-PLA2 in an in vitro adipocyte model.MethodsAnalysis of anthropometric and biochemical variables from a cohort of lean (age 44.4 ± 6.2 years; BMI 22.15 ± 1.8 kg/m2, n = 23), overweight (age 45.4 ± 12.3 years; BMI 26.99 ± 1.5 kg/m2, n = 24), obese (age 49.0 ± 9.1 years; BMI 33.74 ± 3.3 kg/m2, n = 32) and type 2 diabetic women (age 53.0 ± 6.13 years; BMI 35.08 ± 8.6 kg/m2, n = 35), as part of an ethically approved study. Gene and protein expression of PLA2 and its isoforms were assessed in adipose tissue samples, with serum analysis undertaken to assess circulating Lp-PLA2 and its association with cardiometabolic risk markers. A human adipocyte cell model, Chub-S7, was used to address the intracellular change in Lp-PLA2 in adipocytes.ResultsLp-PLA2 and calcium-independent PLA2 (iPLA2) isoforms were altered by adiposity, as shown by microarray analysis (p < 0.05). Type 2 diabetes status was also observed to significantly alter gene and protein levels of Lp-PLA2 in abdominal subcutaneous (AbdSc) (p < 0.01), but not omental, adipose tissue. Furthermore, multivariate stepwise regression analysis of circulating Lp-PLA2 and metabolic markers revealed that the greatest predictor of Lp-PLA2 in non-diabetic individuals was LDL-cholesterol (p = 0.004). Additionally, in people with type 2 diabetes, oxidised LDL (oxLDL), triacylglycerols and HDL-cholesterol appeared important predictors, accounting for 59.7% of the variance (p < 0.001). Subsequent in vitro studies determined human adipocytes to be a source of Lp-PLA2, as confirmed by mRNA expression, protein levels and immunochemistry. Further in vitro experiments revealed that treatment with LDL-cholesterol or oxLDL resulted in significant upregulation of Lp-PLA2, while inhibition of Lp-PLA2 reduced oxLDL production by 19.8% (p < 0.05).Conclusions/interpretationOur study suggests adipose tissue and adipocytes are active sources of Lp-PLA2, with differential regulation by fat depot and metabolic state. Moreover, levels of circulating Lp-PLA2 appear to be influenced by unfavourable lipid profiles in type 2 diabetes, which may occur in part through regulation of LDL-cholesterol and oxLDL metabolism in adipocytes.

The effect of Danshen extract on lipoprotein-associated phospholipase A2 levels in patients with stable angina pectoris: study protocol for a randomized controlled trial - the DOLPHIN study

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2), a biomarker of oxidation and inflammation, has been associated with increased coronary artery disease risk. To date, very few studies have examined the Chinese herbal drug Danshen or its extract on Lp-PLA2 in patients with stable angina pectoris. In this study, we aim to investigate the effect of Danshen extract on Lp-PLA2 level in patients with stable angina.Methods/designThis is a randomized, single-blind, placebo-controlled, adaptive clinical trial. A total of 156 patients meeting the eligibility criteria will be randomly assigned to either the Danshen extract (DanshenDuofensuanyan injection and Danshen drop spill) group or the placebo group in a 1:1 ratio. Participants will then undergo treatment with DanshenDuofensuanyan injection or placebo (glucose) during hospitalization, followed by open-label Danshen drop spill (30 pills/day) in Danshen extract group for 60 days after discharge. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. On the basis of the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the serum level of Lp-PLA2 in the Danshen extract group and the placebo group. The secondary outcomes include the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire and the carotid intima-media thickness, which will be measured using ultrasound. Other secondary efficacy and safety outcomes will also be assessed.DiscussionThis study will provide evidence that Danshen extract is beneficial for stable angina and may establish a possible mechanism of Danshen treatment effects on cardiovascular disease. This study may also validate an objective blood test (LP-PLA2 level) for assessing the effectiveness of Danshen therapy in patients with stable angina pectoris.Trial registrationClinicalTrials.gov, NCT02870764. Registered on 13 August 2016.

Effects of fenofibrate on inflammatory cytokines in diabetic retinopathy patients.

The role of cytokines in diabetic retinopathy (DR) and effects of fenofibrate on cytokines were explored by observing changes in serum IL-1β, TNF-α, VEGF, and Lp-PLA2 in different stages of DR and the intervention effect of oral fenofibrate on cytokines.In total, 190 patients with type 2 DR were enrolled and divided into 3 groups: diabetic without retinopathy (NDR) group (n = 30), nonproliferative diabetic retinopathy (NPDR) group (n = 80), and proliferative diabetic retinopathy (PDR) group (n = 80). According to whether or not to accept fenofibrate treatment, NPDR and PDR groups were further divided into the NPDR control (NPDR1) group (n = 40) and the NPDR treatment (NPDR2) group (n = 40), and the proliferative diabetic retinopathy control (PDR1, n = 40) group and the proliferative diabetic retinopathy treatment (PDR2) group (n = 40). At 12 weeks after fenofibrate treatment, serum IL-1β, TNF-α, VEGF, and Lp-PLA2 levels were detected.In PDR and NPDR patients, levels of serum cytokines such as IL-1β (120.56 ± 27.32 pg/mL vs 112.34 ± 19.45 pg/mL vs 82.9 ± 13.8 pg/mL), TNF-α (125.86 ± 25.57 pg/mL vs 109.48 ± 20.15 pg/mL vs 80.7 ± 12.8 pg/mL), VEGF (166.65 ± 37.74 pg/mL vs 148.54 ± 36.27 pg/mL vs 88.97 ± 24.86 pg/mL), and Lp-PLA2 (172.34 ± 45.22 μg/L vs 154.66 ± 40.98 μg/L vs 125.88 ± 38.87 μg/L) were significantly higher than in diabetes patients without retinopathy. After fenofibrate treatment, serum IL-1β, TNF-α, VEGF, and Lp-PLA2 significantly decreased in NPDR and PDR patients.Serum IL-1β, TNF-α, VEGF, and Lp-PLA2 play an important role in occurrence and development of diabetic retinopathy. Fenofibrate can reduce cytokine levels in DR patients and improve inflammatory response.

Correlation between serum inflammatory cytokine levels and fibrous cap thickness of fibrofatty plaque in coronary culprit lesions

Objective: To identify the correlation between serum inflammatory cytokine levels including high sensitive C reactive protein (hs-CRP) and lipoprotein associated phospholipase (Lp-PLA2) and the fibrous cap thickness of fibrofatty plaque in coronary culprit lesions. Methods: Clinical data of 117 patients with selective coronary artery angiography diagnosed coronary artery disease admitted to our hospital from January 2015 to January 2016 were retrospective analyzed. According to type of coronary disease, patients were divided into 3 subgroups: SAP group (containing 47 stable angina patients), UAP group (containing 52 unstable angina patients), and NSTEMI group(containing 18 acute non ST segment elevation myocardial infarction patients). Serum hs-CRP and Lp-PLA2 levels were measured before subsequent procedures. The characteristics of the culprit lesions were detected by optical coherence tomogarpgy(OCT) before interventional treatment, and the correlation between hs-CRP and Lp-PLA2 and the fibrous cap thickness of fibrofatty plaque in coronary culprit lesions were analyzed. Results: (1) The serum levels of hs-CRP (2.13(1.04, 4.75)μg/L vs. 1.02(0.60, 1.29)μg/L and 1.30(1.03, 1.96)μg/L, all P<0.05) and Lp-PLA2 ((394.8±61.4)mg/L vs. (140.1±40.4)mg/L and (284.5±93.6)mg/L, all P<0.05) were significantly higher in NSTEMI group than in SAP group and UAP group, and serum levels of hs-CRP and Lp-PLA2 were significantly higher in UAP group than in SAP group (all P<0.05). (2)The fibrous cap thickness of fibrofatty plaque in coronary culprit lesions were smaller in NSTEMI group and UAP group than in SAP group(50(50, 60)μm and 60(50, 90)μm vs. 130(80, 190)μm, all P<0.05), and there was no significantly difference between NSTEMI group and UAP group(P>0.05). Proportion of thin-cap fibroatheroma plaque(82.35%(14/18) vs. 19.15%(9/47) and 63.46%(33/52), all P<0.05), plaque rupture(55.56%(10/18)vs. 6.38%(3/47) and 28.85%(15/52), all P<0.05) and thrombosis(33.33%(6/18) vs. 4.26%(2/47) and 9.26%(5/52), all P<0.05) were significantly higher in NSTEMI group than in SAP group and UAP group. Proportion of calcifiacation in plaque was lower in NSTEMI group than in SAP group (11.11%(2/18)vs. 42.55%(20/47), P<0.05), and there was no significantly difference between NSTEMI group and UAP group(P>0.05). (3) Pearson correlation analysis showed that serum levels of hs-CRP(r=-0.233, P<0.05) and Lp-PLA2(r=-0.465, P<0.01)were negatively correlated with fibrous cap thickness of fibrofatty plaques. Spearman correlation analysis showed that serum levels of hs-CRP were positively correlated with plaque rupture(r=0.409, P<0.01) and thrombosis (r=0.227, P<0.05), and serum levels of Lp-PLA2 were also positively correlated with plaque rupture(r=0.499, P<0.01) and thrombosis(r=0.263, P<0.01). (4)Multiple logistic regression analysis showed that serum levels of Lp-PLA2 at baseline was independently related to thin-cap fibroatheroma plaque(OR=1.017, P<0.01). Conclusions: The serum levels of hs-CRP and Lp-PLA2 in NSTEMI patients are much higher than that in SAP and UAP patients, higher in UAP patients than in SAP patients. Prevalence of thin-cap fibroatheroma plaque, plaque rupture and thrombosis was significantly higher in the NSTEMI patients, while the prevalence of calcification in plaque is more often in SAP patients. Increased serum levels of Lp-PLA2 are independent risk factor of thin-cap fibroatheroma plaque formation.

Chronic apical periodontitis as risk factor atherosclerosis and artery disease

Periodontitis is caused by bacteria that are present in periodontal tissues also under physiological condition. Neglected hygiene may increase the number of microorganisms and the formation of chronic apical periodontitis (CAP). The aim of the study was to evaluate changes in inflammatory expression (hsCRP and LpPLA2 in adult patients one year after the end of endodontic treatment, thereby the risk analysis of cardiovascular disease. Material and methods: Twenty-six patients who had history of inflammation outside the oral cavity were diagnosed with CAP before the treatment and one year after the end of endodontic treatment. The studied men and women were divided into two age groups: 50 above years (N = 13) and below 50 years (N = 13). In addition, the study groups were separated in relation to apoAI concentration, taking a cut-off of 150mg/dl. The therapeutic effect was achieved in 26 patients after endodontic treatment. The concentration of bio- chemical parameters – hsCRP and LpPLA2 as well as apoAI was evaluated using the commercially available methods. Statistical analysis was performed using the pair test for dependent samples. Results: In patients below 50 years of age and 1 year after the end of treatment a significant reduction in hsCRP and LpPLA2 level was observed. Similarly, a statistically significant decrese in LpPLA2 concentration was observed in patients with apoAI&gt;150 mg/dl. Conclusions: In patients &lt; 50years of age, after 1 year CAP treatment, the CAP inflammatory foci CAP were reduced and the inflammatory markers were normalized. Also in patients with a high apoAI level, reduced and the after treat suggested that elevated level of apoAI and LpPLA2 in HDL particles might reduce the inflammatory lesion size in CAP and might systemic complications. CAP, particularly in patients over 50 years of age and at an apoAI&lt;150mg/dl and higher level of LpPLA2, is a risk factor for atherosclerosis and destabiliza- tion of atherosclerotic plaque. Endodontic treatment should be induced in medication of atherosclerosis and its complications both in primary and secondary prevention.

Abstract TP125: Distinct Roles of Endothelial Dysfunction and Inflammation in Intracranial Atherosclerotic Stroke

Aims: Endothelial dysfunction and inflammation play a major role in the progression of atherosclerosis. This study aimed to evaluate the differential roles of endothelial dysfunction and inflammation in intracranial atherosclerotic stroke (ICAS). Methods: We prospectively recruited 262 patients with acute cerebral infarcts caused by ICAS and 75 individuals with no history of stroke as controls. Markers of endothelial dysfunction (asymmetric dimethylarginine, ADMA) and inflammation (lipoprotein-associated phospholipase A2, Lp-PLA 2 ) were measured. Acute ischemic lesions were measured in terms of their size, composition, and patterns. Subclinical microangiopathy (degree of leukoaraiosis) and macroangiopathy (presence/number of tandem stenoses) were graded in each patient. Results: Compared to normal controls, serum levels of ADMA (0.69 ± 0.14 vs. 0.47 ± 0.10, P &lt; 0.001) and Lp-PLA 2 (138.1 ± 116.8 vs. 19.0 ± 58.0, P &lt; 0.001) were elevated in patients with ICAS. Although there was a significant correlation between ADMA and Lp-PLA 2 levels in patients with ICAS (r 2 = 0.235, P &lt;0.001), some patients showed high Lp-PLA 2 but low ADMA levels, while others showed high ADMA but low Lp-PLA 2 levels. A high ADMA serum level was associated with a greater prevalence of preclinical microangiopathy and macroangiopathy. Contrastingly, an elevated serum Lp-PLA 2 level was associated with larger ischemic lesions, a greater number of lesions, and a larger cortical pattern. Conclusion: Endothelial dysfunction and inflammation have distinct effects in ICAS patents: endothelial dysfunction is associated with the underlying micro- and macro-atherosclerotic burden, whereas inflammation is associated with acute infarct volume and pattern.

Altered Monocyte and Endothelial Cell Adhesion Molecule Expression Is Linked to Vascular Inflammation in Human Immunodeficiency Virus Infection.

Background.Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium.Methods.Monocyte subsets (CD14+CD16−, CD14+CD16+, CD14DimCD16+) from HIV negative (HIV−) and antiretroviral therapy-treated HIV positive (HIV+) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration. Plasma markers of monocyte (soluble [s]CD14, sCD163) and EC (VCAM-1, ICAM-1,2, fractalkine) activation and systemic (tumor necrosis factor receptor [TNFR-I], TNFR-II) and vascular (lipoprotein-associated phospholipase A2 [Lp-PLA2]) inflammation were measured by enzyme-linked immunosorbent assay.Results.Proportions of CD16+ monocyte subsets were increased in HIV+ participants. Among all monocyte subsets, levels of LFA-1 were increased and CX3CR1 levels were decreased in HIV+ participants (P < .01). Levels of sCD163, sCD14, fractalkine, ICAM-1, VCAM-1, TNFR-II, and Lp-PLA2 were also increased in HIV+ participants (P < .05), and levels of sCD14, TNFR-I, and TNFR-II were directly related to ICAM-1 and VCAM-1 levels in HIV+ participants. Expression of CX3CR1 on monocyte subsets was inversely related to plasma Lp-PLA2 (P < .05 for all).Conclusions.Increased proportions of CD16+ monocytes, cells with altered adhesion molecule expression, combined with elevated levels of their ligands, may promote vascular inflammation in HIV infection.

Higher Levels of Lipoprotein Associated Phospholipase A2 is associated with Increased Prevalence of Cognitive Impairment: the APAC Study

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a unique circulating phospholipase with inflammatory and oxidative activities and the limited data regarding the relationship between Lp-PLA2 and cognitive impairment are conflicted. We conducted a cross-sectional study including 1,374 Chinese adults recruited from 2010 to 2011, aiming to evaluate the relationship between Lp-PLA2 levels and the prevalence of cognitive impairment in a Chinese community-based population. Participants underwent standardized evaluation. Serum Lp-PLA2 mass was measured by ELISA. Cognition status was evaluated via the Mini-Mental Status Exam (MMSE) and cognitive impairment was identified as MMSE <24. Multivariable logistic regression models were used to assess the associations of Lp-PLA2 mass with cognitive impairment. Lp-PLA2 mass was significantly associated with the prevalence of cognitive impairment after adjusting for other potential confounding factors (compared with the first quartile, adjusted ORs of the second, third, and fourth quartile were 2.058 (95% CI, 0.876–4.835), 2.834 (95% CI, 1.255–6.398), and 4.882 (95% CI, 2.212–10.777), p < 0.0001). In conclusion, elevated level of Lp-PLA2 mass was independently associated with the prevalence of cognitive impairment in Chinese adults.

No relationship between lipoprotein-associated phospholipase A2, proinflammatory cytokines, and neopterin in Alzheimer's disease

ObjectiveLipoprotein-associated phospholipase A2 (Lp-PLA2) is a reported risk factor for dementia. However, the relationship between Alzheimer's disease (AD) and Lp-PLA2 is still debatable and, to the best of our knowledge, no study has evaluated the associations between levels of Lp-PLA2, proinflammatory cytokines, and neopterin in AD. MethodsIn total, 59 patients with AD and 38 non-demented individuals were included in the case–control study. Fasting serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), neopterin, and Lp-PLA2 were determined using ELISA. The associations between AD and each of the variables were analyzed by logistic regression. ResultsThe median Lp-PLA2 levels in AD and controls were similar (P=0.29, not significant). Median serum neopterin and IL-6 levels were significantly higher in patients with AD than in controls (P=0.0001 and P=0.03, respectively). In regression analyses, median neopterin levels, a lower level of education, and female gender were significantly associated with AD when compared with controls (OR, 31.44, 95% CI 3.59–275.28, P=0.002; OR, 4.35, 95% CI 1.13–16.61, P=0.032; OR, 7.25, 95% CI 1.88–28.00, P=0.004, respectively). ConclusionIn contrast to previous evidence suggesting its role in dementia and AD, Lp-PLA2 enzyme levels were higher in the controls, and no relationship between Lp-PLA2 and either proinflammatory cytokines or neopterin was identified in AD. Elevated neopterin levels may be considered inflammatory markers of AD.

Metabolic Syndrome and Selective Inflammatory Markers in Psoriatic Patients.

The presented article studies the role of selected inflammatory and anti-inflammatory serum markers of psoriatic patients in the pathogenesis of metabolic syndrome (MS) and psoriasis. The study is based on the comparison between the group of psoriatic patients (74) and the control group (65). We found significantly higher BMI (p < 0.05) and diastolic blood pressure (p < 0.05) in the psoriatic patients. The values of waist circumference and BMI were significantly higher (p < 0.05) in the male patients compared to the men in the control group. The analysis revealed significantly higher CRP (p < 0.001), Lp-PLA2 (p < 0.001), leptin (p < 0.01), and resistin (p < 0.01) levels in the psoriatic patients. Significantly higher levels of CRP (p < 0.01), Lp-PLA2 (p < 0.001), leptin (p < 0.01), and resistin (p < 0.05) were found in the patients with MS compared to the controls with MS. The level of adiponectin was significantly lower (p < 0.01) in the patients with MS. Finally, we found significantly higher level of Lp-PLA2 (p < 0.001) in the group of patients without MS compared to the controls without MS. In conclusion, observed inflammatory and anti-inflammatory markers (CRP, adiponectin, leptin, resistin, and Lp-PLA2) are involved in both pathogenesis of MS and pathogenesis of psoriasis. The level of Lp-PLA2 indicates the presence of subclinical atherosclerosis (cardiovascular risk) in psoriatic patients.

Lipids and lipoproteins and inflammatory markers in patients with chronic apical periodontitis.

BackgroundSince chronic apical periodontitis (CAP) appears to be a risk factor for coronary heart disease, the aim of the study was to determine the relationship between the size of CAP lesion and inflammatory markers (hsCRP, IL-6, TNF-α), as well as lipids and lipoproteins (LpPLA2, apoAI, apoB level) in blood serum of patients with CAP.MethodsThe patients studied (n = 43) were divided into groups: patients under 50 and over 50 years of age, and a separate subgroup of the oldest age with the largest size of CAP lesions. Apolipoprotein AI (apoAI) above 150 mg/dL and below 150 mg/dL was used as an important criterion for the division of patients into groups. The CAP lesion size was measured using the Kodak digital imaging system software. The control group consisted of clinically healthy volunteers (n = 20) without CAP. Lipids were measured on a Siemens analyzer (Germany), apoAI, apoB, hsCRP levels were determined by immunonephelometric method, using the Health Care Diagnostic Product (Siemens GmbH, Germany), and IL-6, TNF-α and LpPLAG7 assay kits (ELISA, R&D Systems) were used.ResultsThe findings suggested that in patients with CAP and their age increase, the CAP lesion size, the concentration of inflammatory markers and LpPLA2 mass increased. Correlations between the CAP lesion size and LpPLA2 mass and between the CAP lesion size and TG level in patients with apoAI 150 ≤ mg/dL showed increase TG in atherogenic apoB-containing triglyceride-rich lipoprotein and TC in cholesterol-rich lipoprotein. The patients with a low apoAI and high LpPLA2 level can have a higher risk of odontogenic disease and progression of atherosclerosis and coronary heart disease.ConclusionWe have found a positive correlation between apoAI level and the CAP lesion size and a negative correlation between LpPLA2 level and the CAP lesion size. The results suggest that apoAI and LpPLA2 in HDL particles have antiinflammatory action and together can limit the CAP lesion size in patient with a higher apoAI level. The literature data on the distribution of lipoprotein particles in subjects are still insufficient, so this problem requires further studies.

Lipoprotein-associated phospholipase A2 and coronary heart disease

Lp-PLA2 is widely concerned in recent years as a vascular inflammation factor that plays an important role in the development of atherosclerosis . The level of plasma Lp-PLA2 is related to the stability of carotid artery atherosclerotic plaque. it is an independent predictor of coronary heart disease risk.Its specific inhibitor Darapladib also becomes a hotspot of clinical cardiovascular pharmaceutical research.However, two randomized, placebo-controlled, double-blind, international, multicenter, event-driven trials, STABILITY and SOLID-TIMI 52, have shown that Darapladib could not significantly reduce the risk of cardiovascular events. (Chin J Lab Med, 2015, 38: 493-497) Key words: Lp-PLA2; CHD; Atherosclerosis; Darapladib

Lp-PLA2 levels are independant of statin treatment in dyslipidemic patients

Lp-PLA2 levels are independant of statin treatment in dyslipidemic patients

Polisaccharide peptide of Ganoderma lucidum against atherogenesis by reduce foam cells and perivascular adiposite

Background: Atherogenesis is an inflammation process, begin with accumulation of oxidized LDL and formation of foam cells. Lingzhi (Ganoderma lucidum) is a woody mushroom, widely consumed as traditional medicine in the belief that it lowers risk of heart diseases and boosts the immune system. Objective: To evaluate the effects of polysaccharide peptide (PsP) of the extract of Ganodermalucidum to reduce LpPLA2, foam cells, and peri vascular adiposite. Methods: The study was experimental study design. The 25 atherosclerotic rats were randomly divided into four groups: atherosclerotic models with high-fat diet, low-dose PsP treated group (50 mg/kgBW), medium-dose PsP treated group (150 mg/kgBW), high-dose PsP treated group (300 mg/kgBW), with normal rats used as the control group. The rats was treated for 5 weeks then we measured the serum level of LpPLA2, foam cells count from aorta and thickness of perivascular adiposite. Result: There was no difference level of LpPLA2 between treated group and untreated group (p = 0.802). Foam cells count significantly low in treated groups (p = 0.024). Peri vascular adiposite thickness at normal rats was not significantly different from PsP treated group (300 mg/kgBW). Conclusion: Polysaccharide peptide of Ganoderma lucidum significantly reduced foam cells and peri vascular adiposite in atherosclerotic rats.

Differential Reduction in Monocyte Activation and Vascular Inflammation With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among HIV-Infected Individuals.

Little is known about how different antiretrovirals effect inflammation and monocyte activation in human immunodeficiency virus (HIV) infection. We examined plasma specimens obtained during a randomized, double-blinded trial in antiretroviral therapy (ART)-naive HIV-infected adults which compared the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) with that of efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). From a random sample achieving an HIV type 1 RNA load of <50 copies/mL by week 48, changes over 24 and 48 weeks in levels of biomarkers of monocyte activation (soluble CD14 [sCD14] and soluble CD163 [sCD163]), systemic inflammation (soluble tumor necrosis factor α receptor I [sTNF-RI], interleukin 6 [IL-6], and high-sensitivity C-reactive protein [hsCRP]), and vascular inflammation (lipoprotein-associated phospholipase A2 [Lp-PLA2]) were compared. Multivariable linear regression was used. A total of 200 participants were included. Significant differences favoring EVG/c/FTC/TDF were noted for changes in sCD14, hsCRP, and Lp-PLA2 levels. Factors independently associated with a larger decrease in the sCD14 level included random assignment to receive EVG/c/FTC/TDF, higher baseline sCD14 level, and larger decreases in hsCRP and sCD163 levels; factors associated with a larger Lp-PLA2 decrease included higher baseline Lp-PLA2 and IL-6 levels, smaller increases in total cholesterol and triglycerides levels, a larger decrease in the sCD14 level, and a smaller decrease in the sCD163 level. EVG/c/FTC/TDF led to greater decreases in sCD14, hsCRP, and Lp-PLA2 levels, compared with EFV/FTC/TDF. Randomization group independently predicted the change in sCD14 level, and changes in monocyte activation independently predicted the change in Lp-PLA2 level. There appears to be a more favorable effect of the integrase inhibitor EVG over efavirenz on immune activation, which may affect vascular inflammation.