Search

Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) plays important roles in inflammation and anaphylaxis. However, its primary function in pancreatic cancer remains unclear. In the current study, we report that PAFAH1B2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and correlated inversely with patient survival. PAFAH1B2 overexpression induced epithelial–mesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo. Conversely, silencing PAFAH1B2 inhibited these aggressive phenotypes. Moreover, PAFAH1B2 overexpression in PDAC cells was directly mediated by HIF1a. PAFAH1B2 expression in PDAC clinical specimens correlated positively with HIF1a expression. Overall, our results defined PAFAH1B2 as a target gene of HIF1a and a critical driver of PDAC metastatic behaviors.

International audience; Background and Aim: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a key role in atherosclerosis development. It is considered a marker of increased risk of cardiovascular disease (CVD) and plaque vulnerability. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol and a higher prevalence of early CVD. Our aim was to evaluate the differences in Lp-PLA2 activity in a population of hypercholesterolemic patients with and without definite FH.Methods and Results: Hypercholesterolemic patients were consecutively recruited. Definite FH was defined according to Dutch Lipid Clinic Network criteria ≥8. All patients underwent routine clinical examination and biological assessments and Lp-PLA2 activity was measured in blood samples. Among 469 patients, 118 had a definite diagnosis of FH. Lp-PLA2 activity was significantly higher in definite FH patients compared to non-definite FH patients (206.5 ± 54.5 vs. 180.8 ± 48.4 nmol/min/mL, p < 0.0001). Lp-PLA2 positively correlated with total cholesterol, LDL-C and apolipoprotein B and negatively with HDL-C and apolipoprotein A-1. In multivariate analysis, definite FH diagnosis, LDL-C, HDL-C and statin treatment remained correlates of Lp-PLA2 independently of systolic blood pressure.Conclusions: Lp-PLA2 activity was higher in definite FH than in non-definite FH patients independently of LDL-C levels and statin treatment. These results highlight the particular phenotype of FH subjects among hypercholesterolemic patients. As increased Lp-PLA2 activity suggests, FH patients exhibit higher arterial inflammation that may contribute to their high cardiovascular risk. Our results reinforce the potential beneficial role of statins pleiotropic effects and the need for proper identification and treatment of FH patients.

Background Elevated serum levels of apolipoprotein (apo) C1 may be an early protein marker of metabolic abnormality in women with polycystic ovary syndrome (PCOS). It is not clear, however, whether there are any relationships between the apoC1 rs4420638A/G and -317deletion (H1)/insertion (H2) polymorphisms and PCOS. We investigated the relationship between these two variants and the risk of PCOS, evaluated the genotypic effects on clinical, hormonal and metabolic indexes and plasma platelet-activating factor acetylhydrolase (PAF-AH) activity, and defined the association of apoC1 gene variants with apoE ε2/ε3/ε4 polymorphisms. Methods This is a cross-sectional study of 877 women with PCOS and 761 controls. The apoC1 rs4420638A/G genotype was determined by a Taqman real-time PCR allelic discrimination assay. The apoC1–317H1/H2 and apoE ε2/ε3/ε4 genotypes were measured using PCR and restriction fragment length polymorphism analysis. The clinical, hormonal and metabolic parameters and PAF-AH activity were measured. Results The frequencies of apoC1 rs4420638A/G and -317H1/H2 genotypes and alleles were similar between PCOS and control groups (P > 0.05). However, the rs4420638 G allele was related to increased serum luteinizing hormone, cholesterol and apoB levels, and the ratio of apoB to apoA1 (P

Aims/hypothesis The aim of the study was to examine the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) activity levels and incident diabetic retinopathy and change in retinopathy grade. Methods This was a cohort study of diabetic participants with serum collected at baseline and routinely collected diabetic retinal screening data. Participants with type 2 diabetes from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) cohort were used. This cohort is composed of individuals of white Scottish ancestry from the Tayside region of Scotland. Survival analysis accounting for informative censoring by modelling death as a competing risk was performed for the development of incident diabetic retinopathy from a disease-free state in a 3 year follow-up period (n = 1364) by stratified Lp-PLA2 activity levels (in quartiles). The same analysis was performed for transitions to more severe grades. Results The hazard of developing incident diabetic retinopathy was 2.08 times higher (95% CI 1.64, 2.63) for the highest quartile of Lp-PLA2 activity compared with the lowest. Higher Lp-PLA2 activity levels were associated with a significantly increased risk for transitions to all grades. The hazards of developing observable (or more severe) and referable (or more severe) retinopathy were 2.82 (95% CI 1.71, 4.65) and 1.87 (95% CI 1.26, 2.77) times higher for the highest quartile of Lp-PLA2 activity compared with the lowest, respectively. Conclusions/interpretation Higher Lp-PLA2 levels are associated with increased risk of death and the development of incident diabetic retinopathy, as well as transitions to more severe grades of diabetic retinopathy. These associations are independent of calculated LDL-cholesterol and other traditional risk factors. Further, this biomarker study shows that the association is temporally sensitive to the proximity of the event to measurement of Lp-PLA2. Electronic supplementary material The online version of this article (10.1007/s00125-018-4601-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Cerebral artery stenosis (CAS) is the most important causes of ischaemic stroke. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) plays 2 diverse roles in atherosclerosis (pro‐inflammatory and anti‐inflammatory), and the association between Lp‐PLA2 mass and cardiovascular or cerebrovascular events is inconsistent among previous studies. A cross‐sectional study including 2012 North Chinese adults aged ≥40 years was performed in 2010‐2011 to investigate whether Lp‐PLA2 mass is associated with asymptomatic cerebral artery stenosis (ACAS). Serum Lp‐PLA2 mass was determined by enzyme‐linked immunosorbent assay (ELISA). All participants underwent transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS). The median serum Lp‐PLA2 mass of the participants was 140.74 ng/mL (interquartile range: 131.79‐158.07 ng/mL). The adjusted odds ratio (OR) when comparing the 4th quartile to the 1st quartile of Lp‐PLA2 was 1.98 (95% confidence interval (CI): 1.42‐2.78), 1.79 (95% CI: 1.08‐2.94) and 1.87 (95% CI: 1.28‐2.73) for the occurrence of ACAS, asymptomatic ECAS and asymptomatic ICAS, respectively, after controlling for vascular risk factors. These independently significant associations remained statistically significant in the male or elderly subgroups, but not in females or middle‐aged participants. Lp‐PLA2 mass is positively correlated with subclinical atherosclerosis determined by ACAS, ICAS and ECAS in North Chinese, particularly in male and older participants, suggesting that serum Lp‐PLA2 mass might be potential biomarker for the detection of ACAS in the adults.

Objective We present prenatal diagnosis and molecular cytogenetic characterization of 17p13.3 microdeletion encompassing YWHAE and CRK but not PAFAH1B1 in a fetus without ultrasound abnormalities. Case report A 33-year-old woman underwent amniocentesis at 17 weeks of gestation because of a family history of spinocerebellar atrophy in the husband. Amniocentesis revealed a karyotype of 46,XX. Simultaneously array comparative genomic hybridization (aCGH) analysis (using 60,000 probes) revealed a 0.7-Mb 17p13.3 microdeletion or arr 17p13.3 (1,264,243–1,965,733) × 1 dn [GRCh37 (hg19)] encompassing YWHAE and CRK but not PAFAH1B1. Prenatal ultrasound findings were unremarkable. There were no structural abnormalities of the brain, heart, kidneys, skull, limbs and other internal organs. The parents elected to terminate the pregnancy, and a 268-g fetus was delivered at 19 weeks of gestation with mild facial dysmorphism. Postnatal high-resolution aCGH analysis of the placenta (using 630,000 probes) showed a 0.79-Mb 17p13.3 microdeletion or arr 17p13.3 (1,173,549–1,970,690) × 1 (hg19) encompassing TUSC5, YWHAE, CRK and HIC1 but not PAFAH1B1. Metaphase fluorescence in situ hybridization analysis using the 17p13.3-specific probe of RP11-818O24 revealed a 17p13.3 deletion. Conclusion Fetus with 17p13.3 microdeletion without involving PAFAH1B1 may present no brain abnormalities on fetal ultra sound.

Protein tyrosine nitration (PTN) is a post translational event which results in the generation of 3-Nitrotyrosine (3-NT). High levels of 3-NT were reported in several human diseases such as Parkinson's disease, Alzheimer's disease, amylotrophic lateral sclerosis and coronary artery disease. It was reported that PTN at positions 307 and 335 of Lipoprotein-associated phospholipase A2 (Lp-PLA2) curtails its enzymatic activity but the mechanism of inhibition at the structure level is still incomprehensible. The present study is an in silico endeavor to understand nitrative stress induced structural changes in Lp-PLA2. Molecular docking studies revealed a decreased binding affinity of substrate, Platelet Activating Factor (PAF) with the nitrated forms of Lp-PLA2 (NT-Tyr307 and NT-Tyr335) compared to the wild type, due to differences in the hydrogen bond interaction patterns. Molecular dynamics (MD) simulation studies suggests higher flexibility of nitrated forms compared to wild type, disorientation of the catalytic triad and decreased molecular interactions of NT-Tyr307 and NT-Tyr335 with other residues of the protein. Essential dynamics (ED) further confirmed the enhanced structural flexibility of nitrated forms of Lp-PLA2. Our findings would help understand the molecular mechanism of nitrative stress induced inhibition of Lp-PLA2 which may further assist in designing of therapeutics having protective functions against PTN.

Background: Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance. Methods: A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score 54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed. Results: The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score 54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = –0.149, and r = –0.085, all P > 0.05; respectively). Conclusions: The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.

This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining. Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). An automatic biochemical analyzer was used to measure the serum levels of biochemical indicators, and homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. Western blot was applied to determine levels of inflammatory cytokines. Compared with Control group, rats in the STZ + saline group were significantly decreased in body weight, the number of embryo implantation, the number of insulin positive cells and pancreatic islet size as well as the islet endocrine cells, and high-density lipoprotein (HDL-C) level, but substantially increased in Lp-PLA2, low-density lipoprotein (LDL-C), fatty acids (FFA), serum total cholesterol (TC), triglyceride (TG) levels. Moreover, the increased fasting plasma glucose (FPG) and HOMA-IR and inflammatory cytokines but decreased fasting insulin (FINS) and ISI were also found in diabetic pregnant rats. On the contrary, rats in the darapladib-treated groups were just opposite to the STZ + saline group, and STZ + High-dose group improved better than STZ + Low-dose group. Thus, darapladib can improve lipid metabolism, and enhance insulin sensitivity of diabetic pregnant rats by regulating inflammatory cytokines.

Background and aims Results from prospective studies evaluating the relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and incident peripheral arterial disease (PAD) have been mixed. We investigated whether higher Lp-PLA2 levels are associated with increased risk of incident PAD and whether PLA2G7 gene variants, which result in lower Lp-PLA2 levels, are associated with reduced risk of incident PAD. Methods Our analysis included 9922 participants (56% female; 21% African-American; mean age 63 years) without baseline PAD at ARIC Visit 4 (1996–1998), who had Lp-PLA2 activity measured and were subsequently followed for the development of PAD, defined by occurrence of a PAD-related hospitalization, through 2012. Cox proportional hazard models were performed to determine the association of Lp-PLA2 levels and PLA2G7 gene variants with incident PAD. Results During a median follow-up of 14.9 years, we identified 756 incident cases of PAD. In analyses adjusting for age, race, and sex, each standard deviation increment in Lp-PLA2 activity (62 nmol/ml/min) was associated with a higher risk of developing PAD (hazard ratio (HR) 1.17; 95% confidence interval (CI) 1.09, 1.26). This association remained significant after additional adjustment for risk factors, other cardiovascular disease, and medication use, but was strongly attenuated (HR: 1.09; 95% CI 1.00, 1.20). PLA2G7 variants were not associated with a lower risk of PAD in both white carriers (HR: 1.21; 95% CI: 0.17–8.56) and African-American carriers (HR: 0.83; 95% CI: 0.41–1.67), although statistical power was quite limited for this analysis, particularly in whites. Conclusions While higher Lp-PLA2 activity was associated with an increased risk for incident PAD, it is likely a risk marker largely represented by traditional risk factors.

Somatic mutation of the lissencephaly-1 gene is a cause of subcortical band heterotopia ("double cortex"). The severity of the phenotype depends on the level of mutation in brain tissue. Detecting and quantifying low-level somatic mosaic mutations is challenging. Here, we utilized droplet digital PCR, a sensitive method to detect low-level mutation. Droplet digital PCR was used in concert with classic genotyping techniques (SNaPshot assays and pyrosequencing) to detect and characterize the tissue mosaicism of a somatic mutation (LIS1 c.190A>T; p.K64X) in a patient with posterior bilateral SBH and refractory epilepsy. The high sensitivity of droplet digital PCR and the ability to target individual DNA molecules allowed us to detect the mutation at low level in the brain, despite the low quality of the DNA sample derived from formalin-fixed paraffin-embedded tissue. This low mutation frequency in the brain was consistent with the relatively subtle malformation resolved by magnetic resonance imaging. The presence of the mutation in other tissues from the patient permitted us to predict the timing of mutagenesis. This sensitive methodology will have utility for a variety of other brain malformation syndromes associated with epilepsy for which historical pathological specimens are available and specific somatic mosaic mutations are predicted.

The cardiotoxicity of various anticancer therapies, including radiotherapy, can lead to cardiovascular complications. These complications can range from damaging cardiac tissues within the irradiation field to increasing the long-term risks of developing heart failure, coronary artery disease, and myocardial infarction. We analyzed radiation-induced metabolites capable of mediating critical biological processes, such as inflammation, senescence, and apoptosis. Previously, by applying QTOF-MASS analysis to irradiated human fibroblasts, we identified that metabolite sets of lysophosphatidylcholine (LPC) were increased in these cells. In this study, radiation-induced LPC accumulation in human aortic endothelial cells (HAECs) increased reactive oxygen species (ROS) production and senescence-associated-beta-galactosidase staining, in addition to decreasing their tube-forming ability. Knockdown of lipoprotein-associated phospholipase A2 (Lp-PLA2) with small interfering RNA (siRNA) inhibited the increased LPC production induced by radiation, and reduced the radiation-induced cell damage produced by ROS and oxidized low-density lipoprotein (LDL). Lp-PLA2 depletion abolished the induction of proinflammatory factors, such as interleukin 1β, tumor necrosis factor-alpha, matrix metalloproteinase 2, and matrix metalloproteinase 9, as well as adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1) and E-selection. Likewise, we showed that Lp-PLA2 expression was upregulated in the vasculature of irradiated rat, resulting in increased LPC production and LDL oxidation. Our data demonstrate that radiation-induced LPC production is a potential risk factor for cardiotoxicity that is mediated by Lp-PLA2 activity, suggesting that LPC and Lp-PLA2 offer potential diagnostic and therapeutic approaches to cardiovascular damage during radiotherapy.

The aim of the study was to measure platelet-activating factor acetyl hydrolase (PAF-AH) and paraoxonase (PON1) enzyme activity levels in patients with high Psa values to compare with healthy peers and also to determine the efficacy of these parameters in predicting pathologic results of patients with high Psa values. This study included 66 patients with Psa value > 4 ng/dl (Group 1) and 44 patients with Psa

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent risk factor for cardiovascular disease. Accordingly, studies from many countries around the world have shown an association between Lp-PLA2 and cardiovascular events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), but this association has not been documented among the Chinese. The aim of this study was to assess the use of Lp-PLA2 as a useful marker for predicting the long-term prognosis of Chinese patients with ACS undergoing PCI. A total of 651 consecutive patients undergoing PCI between September 2013 and January 2015 were divided into 2 groups: the high Lp-PLA2 group (n = 262, Lp-PLA2 > 138 nmol/L) and the low Lp-PLA2 group (n = 389, Lp-PLA2 ≤ 138 nmol/L). The end point was all-cause mortality and rehospitalization. The median follow-up was 24 months. Multivariate analysis showed that high Lp-PLA2 was an independent predictor of all-cause mortality and rehospitalization (hazard ratio: 1.429, 95% confidence interval [CI]: 1.411-1.448; P < .05). The Lp-PLA2 had good accuracy for predicting all-cause mortality and rehospitalization among patients with ACS undergoing PCI (area under the receiver–operating characteristic curve: 0.858, 95% CI: 0.819-0.898; P < .05), and a good correlation with the Global Registry of Acute Coronary Event score ( r = 0.525, P < .05). This study provided evidence that Lp-PLA2 could predict all-cause mortality and rehospitalization risk among patients with ACS undergoing PCI.

This study investigated the associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risks of coronary heart disease (CHD) and ischemic stroke (IS) in the general population.PubMed, Embase, and the Cochrane Library databases were searched for prospective cohort studies published prior to June 2016. Multivariate-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CHD and IS risks according to Lp-PLA2 activity or mass were extracted, pooled, and weighted using random-effects modeling.Twelve studies examining Lp-PLA2 activity or mass and long-term risks of CHD and IS were included. Combined HRs for CHD and IS risks for the highest category referring to lowest category of Lp-PLA2 were 1.46 (95% CI: 1.20-1.78, P0.001) and 1.58 (95% CI: 1.21-2.07, P=0.001), respectively. The same patterns were observed for both mass and activity, with the exception of those for CHD. For every 1-standard deviation (SD) increase in Lp-PLA2 activity, CHD risk increased by 12% (HR: 1.12, 95% CI: 1.05-1.22, P=0.002); no association between 1-SD increases in Lp-PLA2 activity and IS was observed. Lp-PLA2 mass was associated with CHD risk (HR: 1.02-1.24, 95% CI: 1.02-1.24, P=0.021). Lp-PLA2 mass per 1-SD increase was not associated with IS risk.Greater Lp-PLA2 activity or mass was associated with an increased risk of CHD and IS; however, additional well-designed trials are warranted to confirm this association.

Aim To investigate the RBP4/Lp-PLA2/Netrin-1 signal regulation of cognitive function impairment in diabetic nephropathy patients with silent cerebral infarction (SCI). Methods One-hundred patients newly diagnosed with diabetic nephropathy patients were included. The patients were divided into SCI group and NSCI group according to the radiological data. The degrees of cognitive dysfunction were evaluated. Serum RBP4 concentrations were determined by ELISA and protein expressions of Lp-PLA2 and Netrin-1 were determined by Western Blot. Results Compared with NSCI group, the cognitive function of patients in SCI group was impaired, the concentrations of RBP4 and the expressions of Lp-PLA2 and Netrin-1 increased (P Conclusion RBP4 may be used as a predictive factor of diabetic nephropathy patients complicated with SCI and is positively correlated with cognitive dysfunction. RBP4/Lp-PLA2/Netrin-1 pathway activation may be one of the occurrence mechanisms in diabetic nephropathy complicated with SCI.

Cardiovascular risk assessment in patients with diabetes relies on traditional risk factors. However, numerous novel biomarkers have been found to be independent predictors of cardiovascular disease, which might significantly improve risk prediction in diabetic patients. We aimed to improve prediction of cardiovascular risk in diabetic patients by investigating 135 evolving biomarkers. Based on selected biomarkers a clinically applicable prediction algorithm for long-term cardiovascular mortality was designed. We prospectively enrolled 864 diabetic patients of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study with a median follow-up of 9.6 years. Independent risk factors were selected using bootstrapping based on a Cox regression analysis. The following seven variables were selected for the final multivariate model: NT-proBNP, age, male sex, renin, diabetes duration, Lp-PLA2 and 25-OH vitamin D3. The risk score based on the aforementioned variables demonstrated an excellent discriminatory power for 10-year cardiovascular survival with a C-statistic of 0.76 (P

We explored the associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) level and carotid atherosclerosis with all phenotypes and cardiovascular disease (CVD) events in Chinese older adults. A total of 1257 adults aged ≥55 years who were free of CVD were enrolled in this cohort study. Lipoprotein-associated phospholipase A2 level was evaluated in 3 categories: Lp-PLA2 < 175, 175≤ Lp-PLA2 < 223, and Lp-PLA2 ≥ 223 ng/mL. The highest level of Lp-PLA2 was independently associated with common carotid artery intima-media thickening (≥1.0 mm; odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.14-2.26) and carotid plaque (OR: 1.42, 95% CI: 1.01-1.99) in individuals without carotid artery stenosis. At the end of the 5-year follow-up, after adjustment for CVD risk factors and carotid atherosclerosis status, Lp-PLA2 had remained an independent predictor for myocardial infarction (MI; hazard ratio [HR]: 1.90, 95% CI: 1.02-3.55) and CVD death (HR: 1.78, 95% CI: 1.02-3.13). However, no association was found with stroke. Therefore, elevated Lp-PLA2 level in the older adults studied was associated with an increased risk of carotid atherosclerosis and MI and CVD mortality. Lipoprotein-associated phospholipase A2 assessment might be used for MI and CVD death risk prediction.

This case-control study explored correlations between LP-PLA2 gene polymorphisms (A379V, V279F, and R92H) and susceptibility and severity of acute pancreatitis (AP) in a Chinese population.From October 2013 to October 2015, 94 AP patients were chosen as the case group. According to the Acute Physiology and Chronic Health Evaluation (APACHE) II score standard, AP patients were divided into a mild AP (MAP) group (n = 46) and severe AP (SAP) group (n = 48). The 48 SAP patients were further divided into an SAP with multiple organ dysfunction syndrome (MODS) group (n = 42) and SAP without MODS group (n = 6). Meanwhile, 96 healthy subjects who received physical examinations at the study hospitals were selected as the control group. Serum lipoprotein-associated phospholipase A2 (LP-PLA2) levels were detected by an enzyme-linked immunosorbent assay (ELISA). The A379V (s1051931), V279F (rs16874954), and R92H (rs13989) polymorphisms of the LP-PLA2 gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).There were significant differences in the frequencies of the LP-PLA2 gene polymorphisms between the AP group and the control group. The distribution of V279F-AA+AC genotype and R92H-AA+AG genotype in the AP group was higher than that in the control group, whereas the SAP group and SAP with MODS group distributions were higher than those in the MAP group and SAP without MODS group (both p 0.05). G-C-A, G-A-G, and G-C-G haploids formed by A379V, V279F, and R92H may be associated with AP susceptibility. LP-PLA2 gene polymorphisms could affect serum LP-PLA2 level, whereas the V279F-A allele gene, the R92H-A allele gene, serum LP-PLA2 level, and serum amylase may be independent risk factors for AP (all p 0.05).These results demonstrated that the LP-PLA2 gene polymorphisms, V279F and R92H, may be associated with susceptibility to and severity of AP.

Aneurysmal bone cyst (ABC) is a locally aggressive, expansile, typically multilocular cystic bone tumor. ABC was previously thought to be a non-neoplastic lesion; however, it is now considered to be neoplasm that features recurrent chromosomal translocations resulting in gene fusions between ubiquitin specific peptidase 6 (USP6) and multiple partners, including COL1A1, CDH11, TRAP150, ZNF90 and OMD. Using next generation sequencing (NGS), we uncovered two fusion partners of USP6 in two ABCs: platelet activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1), which is known to contribute to tumorigenesis in lung cancer, and runt-related transcription factor 2 (RUNX2), which is known to regulate osteoblastic differentiation, osteosarcoma tumorigenesis and its metastasis. In our study, the PAFAH1B1-USP6 fusion consisted of the promoter of PAFAH1B1 fused to the 5'-untranslated region (5'-UTR) of USP6 and was discovered in a typical ABC. The RUNX2-USP6 fusion had the promoter and a short coding region of RUNX2 fused to the translation start codon of USP6 and was detected in an unusually aggressive ABC with an osteosarcoma-like soft tissue extension. Our findings not only expanded the repertoire of the partner genes of USP6 in ABC but also can serve as a reference for future studies to better understand the correlation between various gene fusions and the progression of ABC.

Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that exhibits proinflammatory properties and has been associated with subclinical cardiovascular disease. Objective The relationship between Lp-PLA2 and subclinical CVD remains unclear. The goal of this systematic review was to clarify this relationship. Methods An extensive literature search of the MEDLINE database using Ovid and PubMed was performed. From an initial search of 444 articles, 13 met the inclusion and exclusion criteria and were included in the review. Results Of the 13 studies included in the review, 6 examined the relationship between Lp-PLA2 and coronary artery calcification, of which 3 showed a significant correlation. Two studies examined the relationship between Lp-PLA2 and endothelial dysfunction, and 1 reported a significant relationship. Five studies investigated the association of Lp-PLA2 with carotid intima-media thickness (CIMT), and 3 reported a significant relationship. Conclusions This review shows a variable association between Lp-PLA2 and subclinical disease. This finding has broad implications for the future of public health and clinical practice. Future research is needed to clarify what role Lp-PLA2 has in guiding treatment and if it is involved in plaque instability, which would make it a useful tool for risk prognostication.

There are limited data on the efficacy and safety of triglyceride (TG)-lowering agents in women. We conducted subgroup analyses of the effects of icosapent ethyl (a high-purity prescription form of the ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid) on TG levels (primary efficacy variable) and other atherogenic and inflammatory parameters in a total of 215 women with a broad range of TG levels (200-2000 mg/dl) enrolled in two 12-week placebo-controlled trials: MARINE (n = 18; placebo, n = 18) and ANCHOR (n = 91; placebo, n = 88). Icosapent ethyl 4 g/day significantly reduced TG levels from baseline to week 12 versus placebo in both MARINE (-22.7%; p = 0.0327) and ANCHOR (-21.5%; p0.0001) without increasing low-density lipoprotein cholesterol levels. Significant improvements were also observed in non-high-density lipoprotein cholesterol levels in MARINE (-15.7%; p = 0.0082) and ANCHOR (-14.2%; p0.0001) and total cholesterol levels in MARINE (-14.9%; p = 0.0023) and ANCHOR (-12.1%; p 0.0001), along with significant increases of500% in eicosapentaenoic acid levels in plasma and red blood cells (all p0.001). Icosapent ethyl was well tolerated, with adverse-event profiles comparable with findings in the overall studies. In conclusion, icosapent ethyl 4 g/day significantly reduced TG levels and other atherogenic parameters in women without increasing low-density lipoprotein cholesterol levels compared with placebo; the clinical implications of these findings are being evaluated in the REDUCtion of Cardiovascular Events With Eicosapentaenoic Acid [EPA]-Intervention Trial (REDUCE-IT) cardiovascular outcomes study.

Background Risk associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and adverse outcomes in patients with coronary heart disease (CHD) remain unclear. The aim of the meta-analysis was to investigate the association between Lp-PLA2 and prognosis of CHD. Methods PubMed and Embase were examined for prospective studies published before June 2016. Multivariate-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of adverse outcomes according to Lp-PLA2 activity or mass were extracted, pooled, and weighted using generic inverse-variance and random-effect modeling. Results Fifteen studies with 30,857 participants were included. Overall, higher Lp-PLA2 activity or mass was not significantly related to increased risk of long-term all-cause mortality. However, higher Lp-PLA2 activity or mass was independently associated with an increased risk of long-term cardiovascular events, with pooled HR for cardiovascular events of 1.55 (95% CI, 1.08–2.23; P = 0.018) and 1.62 (95% CI, 1.09–2.41; P = 0.017), respectively. The prognostic value of Lp-PLA2 in predicting cardiovascular events was observed in patients with stable CHD who were not receiving therapies for inhibiting Lp-PLA2. Conclusions Greater Lp-PLA2 activity or mass was independently associated with cardiovascular events in patients with CHD, particularly in patients with stable CHD who were not receiving therapies for inhibiting Lp-PLA2.

Objective To evaluate the association between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2; known to release inflammatory mediators that promote atherosclerosis) and coronary heart disease (CHD) in Chinese patients. Methods This observational, cross-sectional study included a patient cohort who were assessed by coronary angiography and divided into patients with coronary heart disease and patients with normal coronary angiography (controls). Data for several biochemical indicators were collected. Plasma Lp-PLA2 concentrations were measured by enzyme-linked immunosorbent assay. Univariate and multivariate logistic regression were used to analyse the association between Lp-PLA2 concentration and CHD. Results A total of 531 patients were included, comprising 391 with CHD and 140 with normal coronary angiography (controls). Plasma Lp-PLA2 concentration was significantly higher in patients with CHD versus controls (median, 251 µg/l versus 219 µg/l, respectively), and particularly among patients with acute myocardial infarction and stable angina pectoris (249 µg/l and 266 µg/l, respectively). Multivariate analysis showed that Lp-PLA2 ≥ 292 µg/l (upper quartile of the whole cohort) was independently associated with CHD (odds ratio 2.814, 95% confidence interval 1.519, 5.214). Conclusion Plasma Lp-PLA2 concentration was independently associated with CHD in Chinese patients.

Background/Aims: The aim of the study was 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-PLA2) 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 asymptomatic 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 < 0.001) and Lp-PLA2 (138.1 ± 116.8 vs. 19.0 ± 58.0, p < 0.001) were elevated in patients with ICAS. A high ADMA serum level was associated with greater prevalence of preclinical microangiopathy and macroangiopathy. Contrastingly, an elevated serum Lp-PLA2 level was associated with larger ischemic lesions, a greater number of lesions, and a larger cortical pattern. Conclusions: 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.

BackgroundDiet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation.MethodsA population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991–1994. Plasma suPAR was assessed by ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded.ResultsAfter full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p

Aortic stenosis was first described by the French surgeon and anatomist Lazare Riviere in 1663. While the last decade has seen impressive advances in our ability to treat aortic valve stenosis invasively and percutaneously, significant issues remain with regards to the optimal timing of valve replacement, periprocedural risks and long-term durability. There therefore remains major interest in developing medical treatments to halt or slow progression of aortic stenosis, which could obviate the need for surgical intervention altogether. A stitch in time saves nine; however, no pharmacotherapies are currently proven to be effective for the treatment of calcific aortic valve stenosis (CAVS). Atherogenic apolipoprotein B-containing lipoproteins, such as low-density lipoprotein (LDL) and lipoprotein(a) (Lp(a)), have clearly been implicated in the pathogenesis of aortic stenosis, particularly in the early initiation phase. However, LDL cholesterol lowering with statins or ezetimibe failed to modify progression of aortic valve stenosis in multiple randomised clinical trials (SEAS, SALTIRE and ASTRONOMER). Attention has instead switched to Lp(a), with a growing body of epidemiology, genetics and prospective imaging studies having built a convincing case for elevated Lp(a) levels being associated with an increased incidence of aortic stenosis, …

Background Type 2 diabetes mellitus (T2DM) is a major risk factor of atherosclerosis. Hyperglycemia in T2DM causes advanced formation of glycation end products (AGE) which leads to oxidative stress and chronic inflammation. Oxidative stress occurs due to increased levels of reactive oxygen species (ROS) such as H2O2. On the other hand, lipoprotein-associated phospholipase (Lp-PLA2) has pro-inflammatory effects, which cause instability of atherosclerosis plaques. This condition causes hypoxemic cells to stimulate HIFα induced vasa vasorum angiogenesis. This study aims to understand the potential of PSP as an anti-angiogenic agent through decreased levels of H2O2 and Lp-PLA2 leading to the decline of vasa vasorum angiogenesis in diabetic rat model. In addition, this study also measured the lipid profile of diabetic rat model in relation to vasa vasorum angiogenesis. Methods True laboratory experiment with randomized post-test control of group design using 25 wistar rats (Rattus norvegicus) were divided into five groups; one normal group and four group with High Fat Diet (HFD) and low dose streptozotocin (30 mg/kgBW) injection sc, treated with placebo and three various doses of PSP 50, 150, 300 mg/kgBW. Results ANOVA test (p < 0.05) shows that there is a significant influence of polysaccharide peptide (PSP) feeding on the decreased amount of vasa vasorum angiogenesis (p = 0.00), lipid profile (cholesterol total and triglyceride; p = 0.01, p = 0.001), and amount of H202 (p = 0.003). The amount of Lp-PLA2 declined to (p = 0.184). This result indicates that PSP prevents inflammation in atherosclerosis. Conclusions PSP of Ganoderma lucidum is an anti-angiogenic agent in T2DM.

People with HIV (PWH) have an increased prevalence of cardiovascular disease (CVD) compared to uninfected patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2) catalyzes the synthesis of pro-inflammatory lipids that recruit monocytes. Current guidelines for assessing cardiovascular risk in HIV-infected patients suggest that Lp-PLA2 may be a useful surrogate marker for CVD health in this patient population. Lipoprotein-associated phospholipase A2, lipids, glucose, physical parameters, and carotid intimal–medial thickness (CIMT) were measured in 98 participants (49 HIV-uninfected, 27 antiretroviral therapy [ART]-naive PWH, and 22 ART-treated PWH). HIV viral load (VL) and CD4+ T-cell count were measured in HIV-infected participants. Lipoprotein-associated phospholipase A2 was increased in participants on protease inhibitor (PI) ART (median 50.5 vs 127.0 nmol/mL, P = .05) and correlated with age, body mass index, and cholesterol. Lipoprotein-associated phospholipase A2 was not related to Framingham risk score or CIMT but correlated directly with VL (r = .323, P = .025) and inversely with CD4+ T-cell count (r = −.727, P < .001). Lipoprotein-associated phospholipase A2 was increased in HIV-infected participants on PIs and correlated strongly with VL and CD4+ T-cell count suggesting that HIV-associated inflammation is linked to increased Lp-PLA2, providing a mechanistic link between HIV and CVD.

Objective The aim of this study was to explore the clinical values of combined detection of lipoprotein‐associated phospholipase A2 (Lp‐PLA2), serum amyloid A (SAA), and plasma fibrinogen (FIB) in the diagnosis of acute cerebral infarction (ACI). Methods A case‐control study including 100 hospitalized patients with ACI and 47 healthy controls was carried out. The level of Lp‐PLA2, SAA, and FIB was detected, respectively, and their clinical values were analyzed. Carotid lesions and neurological impairment were also analyzed in each patient. Results The level of Lp‐PLA2, SAA, and FIB in the ACI group was significantly higher than that of the controls, and the three biomarkers showed a significant positive correlation and were considered as risk factors for ACI. The area under the curve (AUC) for Lp‐PLA2, SAA, and FIB was 0.858, 0.743, and 0.672, respectively. When three biomarkers were used in combination, the AUC was 0.879. Compared with the other groups, the levels of three biomarkers in bilateral carotid plaque ACI group were all significantly higher. In addition, the level of Lp‐PLA2 and SAA in ACI patients with severe neurological impairment was also significantly higher than that of the mild‐to‐moderate group. Conclusion Lp‐PLA2 combined with SAA and FIB had a high clinical value for rapid diagnosis and prediction of ACI. These biomarkers were also significantly associated with the formation of bilateral carotid atherosclerotic plaques and the severe neurological impairment in ACI patients.

Objective This study aims to explore the curative effect of dl‐3‐n‐butylphthalide (NBP) on patients with acute cerebral infarction (ACI) and its effects on serum lipoprotein‐associated phospholipase A2 (Lp‐PLA2) and hypersensitive C‐reactive protein (hs‐CRP) levels. Methods A total of 136 ACI patients treated in our hospital, who met the criteria, were selected and randomly divided into two groups: control group (n = 60, including 28 males and 32 females) and treatment group (n = 76, including 32 males and 44 females). Patients in the control group were treated with routine drug therapy, while patients in the treatment group were treated with NBP on this basis. A dose of 100 ml was administered by intravenous injection for 2 times/day, for 14 days. The curative effect was evaluated using the National Institute of Health Stroke Scale (NIHSS) and Barthel index (BI) self‐care ability. The levels of the two factors in serum were measured using enzyme‐linked immunosorbent assay, and the changes in levels of these two factors in serum at different time points before and after treatment were compared between the two groups. Results (a) Lp‐PLA2 and hs‐CRP levels in the treatment group after treatment were significantly lower than those before treatment and those in the control group after treatment (p, Dl‐3‐n‐butylphthalide can improve the expression of Lp‐PLA2 and hs‐CRP in serum in ACI patients. Furthermore, NBP has significant efficacy in inhibiting inflammation and improving neurological symptoms.

Hemodialyzed patients (HD) have high prevalence of peripheral arterial disease. In the general population, lipoprotein-associated phospholipase A2 (Lp-PLA2 ) is associated with peripheral arterial disease but no data are available for renal subjects. The aim of this study was to evaluate the relationship between Lp-PLA2 and lower limb ischemia among dialyzed patients. One hundred and two dialyzed subjects, with median (IQR) age of 71 (59-78) years, enrolled in June 2013 and followed until June 2018, were investigated for Lp-PLA2 activity and the occurrence of peripheral arterial disease and lower limb ischemia. The median (IQR) levels of Lp-PLA2 were 184 nmol/min/mL (156.5-214.5). The 43 HD patients with abnormal Lp-PLA2 activity (>194 nmol/min/mL) had higher levels of total and LDL-cholesterol, ApoB/A1 ratio, and higher occurrence of lower limb ischemia during the follow up (44% vs 17%, P = .003). In multivariate analysis, Lp-PLA2 activity (P = .018) and diabetes (P < .001) were independently associated with time to lower limb ischemia, and when the presence of previous PAD was added to the multivariate model, only presence of previous PAD (P < .001) and Lp-PLA2 (P = .003) remained associated. Lp-PLA2 is an independent predictor of lower limb ischemia in dialyzed patients.

The short arm of chromosome 17 is characterized by a high density of low copy repeats, creating the opportunity for non-allelic homologous recombination to occur. Microdeletions of the 17p13.3 region are responsible for neuronal migration disorders including isolated lissencephaly sequence and Miller-Dieker syndrome. We describe the case of a 4-year and 2-month-old female with peculiar somatic traits and neurodevelopmental delay. At the age of 6 months, she started to present with infantile spasms syndrome; therefore, we administered vigabatrin followed by two cycles of adrenocorticotropic hormone, with good response. The coexistence of epileptic activity, neuropsychological delay, brain imaging abnormalities, and peculiar somatic features oriented us towards the hypothesis of a genetic etiology that could explain her clinical picture. Array CGH identified a 730 Kb deletion in the p13.3 region of the short arm of chromosome 17 including eleven genes, among these are YWHAE and CRK. Microdeletions of the 17p13.3 region involving only YWHAE and CRK, sparing PAFAH1B1, result in neurodevelopmental delay, growth retardation, craniofacial dysmorphisms, and mild structural brain abnormalities. Differently from the previously described patients carrying YWHAE and CRK deletions, the main complaint of our patient was represented by seizures. The absence of clear neuronal migration defects and mutations of the PAFAH1B1 gene in our patient underlines the central role of additional genes located in the 17p13.3 chromosomal region in the pathogenesis of epilepsy and helps to expand the phenotype of 17p13.3 microdeletion syndrome.

Background Increased serum Lp‐PLA2 levels have been reported in patients who experienced an ischemic stroke; however, the relationship between Lp‐PLA2 and H‐type hypertension in patients with ischemic stroke remains unclear. Methods In the present study, we investigated the correlation between serum Lp‐PLA2 and H‐type hypertension in patients with ischemic stroke. A total of 135 patients who experienced acute ischemic stroke were enrolled in Tianjin Huanhu Hospital during October 2015 to May 2016. The demographic characteristics of the patients were collected, and biochemical parameters were detected. Results Among the 135 patients, 111 patients had essential hypertension, including 41 patients with H‐type hypertension and 70 with non‐H‐type hypertension. There were higher proportions of males and patients with diabetes mellitus in the H‐type hypertension group compared with the non‐H‐type hypertension group (P 208.46 mg/L were independently associated with H‐type hypertension in patients with ischemic stroke (OR: 2.560, 95% CI: 1.085‐6.040, P = .032). The area under the ROC curve of Lp‐PAL2 levels in the H‐type hypertension group was 0.665 (95% CI: 0.561‐0.768, P = .004). Conclusion Synergetic effects of H‐type hypertension and Lp‐PLA2 levels were noted in the pathogenesis of ischemic stroke.

Acute ST-segment elevation myocardial infarction (STEMI) is the most lethal coronary heart disease with vascular endothelium dysfunction and inflammation in the disease development process. Endothelial cell-specific molecule 1 (ESM-1) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are important for the diagnosis and characterization of STEMI. To date, no studies have reported the correlation between ESM-1 and Lp-PLA2 levels in patients with STEMI, which may be an important predictor of the fatal disease. To measure the level of serum ESM-1 and Lp-PLA2, and to evaluate the relationship and the clinical significance of these two biomarkers in patients with acute STEMI, 37 inpatients with acute STEMI were sequentially enrolled in the research group and 24 study objects with normal coronary artery function were included in the control group. The measurement of the relative parameters was done by enzyme-linked immunosorbent assay using blood samples taken from the median cubital vein while the inpatients were enrolled. The levels of serum SEM-1 and Lp-PLA2 were significantly higher in patients with acute STEMI than in study objects with normal coronary artery function (P

The increased risk of cardiovascular disease under hypercholesterolemia is due to associations between oxidized low-density lipoprotein (ox-LDL) and lipoprotein-associated phospholipase AOne hundred thirty-one subjects with borderline hypercholesterolemia (serum cholesterol ≥200 mg/dL) were divided into low ox-LDL (n = 66) and high ox-LDL (n = 65) groups. After adjusting for confounding factors, the high ox-LDL group exhibited a significantly decreased activated partial thromboplastin time (aPTT) and prothrombin time (PT) and increased Lp-PLAHigh ox-LDL levels may be involved in the development of a procoagulant state in subjects with borderline hypercholesterolemia by increasing Lp-PLA

Background While Miller-Dieker syndrome critical region deletions are well known delineated anomalies, submicroscopic duplications in this region have recently emerged as a new distinctive syndrome. So far, only few cases have been described overlapping 17p13.3 duplications. Methods In this study, we report on clinical and cytogenetic characterization of two new cases involving 17p13.3 and 3p26 chromosomal regions in two sisters with familial history of lissencephaly. Fluorescent In Situ Hybridization and array Comparative Genomic Hybridization were performed. Results A deletion including the critical region of the Miller-Dieker syndrome of at least 2,9 Mb and a duplication of at least 3,6 Mb on the short arm of chromosome 3 were highlighted in one case. The opposite rearrangements, 17p13.3 duplication and 3p deletion, were observed in the second case. This double chromosomal aberration is the result of an adjacent 1:1 meiotic segregation of a maternal reciprocal translocation t(3,17)(p26.2;p13.3). Conclusions 17p13.3 and 3p26 deletions have a clear range of phenotypic features while duplications still have an uncertain clinical significance. However, we could suggest that regardless of the type of the rearrangement, the gene dosage and interactions of CNTN4, CNTN6 and CHL1 in the 3p26 and PAFAH1B1, YWHAE in 17p13.3 could result in different clinical spectrums.

Lipoprotein-associated phospholipase ATo assess the effect of extended-release niacin (ERN) on Lp-PLAWe performed a post hoc analysis in 3196 AIM-HIGH patients with established CV disease and low baseline levels of high-density lipoprotein cholesterol (HDL-C) who were randomized to ERN versus placebo on a background of simvastatin therapy (with or without ezetimibe) to assess the association between baseline Lp-PLAParticipants randomized to ERN, but not those randomized to placebo, experienced a significant 8.9% decrease in LpPLAAmong participants with stable CV disease on optimal medical therapy, elevated Lp-PLA

Although numerous studies have evaluated the association between lipoprotein associated phospholipase A2 (Lp-PLA2) gene polymorphisms and coronary heart disease, the conclusions are still inconsistency. Here we detected the correlation between D166E polymorphism of Lp-PLA2 and myocardial infarction (MI). Further, its clinical value as biomarker was assessed.A total of 297 patients were enrolled, all diagnosed as MI at the Hebei General Hospital between May 2017 and May 2018, with 262 healthy subjects recruited as controls. Blood specimens of all participants were collected for testing serum lipid, blood glucose, Lp-PLA2, HsCRP, IL-17 and IL-35. The D166E polymorphism was genotyped. The correlation between D166E polymorphism and MI was explored using multiple logistic regression analysis.We detected higher levels of TC, TG, LDLC, Lp-PLA2, HsCRP and IL-17 but lower levels of HDLC and IL-35 in MI patients, compared with healthy controls (p0.05). Also, the positive ratio of family history is higher in MI patients than that in control. Indexes were collected after one-week and one-month hospitalization, respectively, and levels of Lp-PLA2, HsCRP, IL-17 and IL-35 decreased to the normal levels (p0.05). We also observed positive correlations between Lp-PLA2 with HsCRP and IL-17 (r=0.6517, 0.2689), and negative correlations between IL-35 with Lp-PLA2, HsCRP and IL-17 (r=-0.3142, -0.3968, -0.2516), respectively. The G allele at D166E accounted for a higher percentage in MI patients than in controls, and so as the GG and GC genotypes (p0.05). Logistic regression analysis showed close associations between MI with Lp-PLA2 and GG genotype at D166E, with odds ratios of 1.239 (1.023-2.017) and 9.863 (4.107-21.331), which suggested they were independent risk factors for the development of coronary heart disease.The D166E (C/G) mutation of Lp-PLA2 was a potential risk factor of MI.

Dyslipidemia and dyslipoproteinemia are common causes of metabolic and cardiovascular diseases. On the other hand, intracellular bacteria, such as Borrelia burgdorferi, utilize host lipids to survive and disseminate within the host. Recent data suggest that elevated lipids are a contributing factor to the maintenance and severity of Lyme disease and its complications. Here we review and discuss the role of lipids in Borreliosis and report on a pilot trial to examine the potential roles of circulating lipids and lipoproteins in patients with Borrelia infection. In this analysis we assessed the clinical and lipid profiles of 519 patients (319 women, 200 men) with a proven history of Lyme disease, before and after an extracorporeal double membrane filtration. Lipid profiles pre- and post-apheresis were analyzed in conjunction with clinical symptoms and parameters of inflammation. Circulating cholesterol, triglycerides, LDL, LP(a), and other inflammatory lipids were significantly reduced after the apheresis, while symptoms of the disorder and bioindexes of inflammation such as CRP improved. Further studies should be initiated to investigate the possibly causal relation between Lyme disease and circulating lipids and to design appropriate therapeutic strategies.

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a well- known risk factor of atherosclerotic vascular diseases which are common comorbidities in psoriasis. The aim of this study was...

To explore the regulation of PLA2G7 silencing on myocardial fibrosis in mice with coronary atherosclerosis, we established model of atherosclerosis using ApoE knockout mice, and set up a normal group. The successfully modeled mice were assigned into the following three groups: PLA2G7 silencing (shRNA) group, negative control (NC) group and blank group. Peripheral blood and myocardial tissue of each group of mice were harvested. The expressions of serum total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in mice were determine using Elisa, and the atherosclerosis index was calculated. The pathological changes of myocardial tissue were observed after HE staining. The collagen volume fraction in myocardium was determined with the use of Masson staining. The expression of PLA2G7 in myocardial tissue as well as myocardial fibrosis markers C-reactive protein, interleukin-6 and intercellular adhesion molecule-1 in each group were detected by qRT-PCR and Western blot. The area of thoracic aorta injury was detected after oil red O staining. Compared with the normal group, the levels of total cholesterol, triglyceride and LDL-C were increased, HDL-C levels were decreased, and atherosclerosis index was increased in the PLA2G7 shRNA group, NC group and blank group (all P 0.05). The pathological state of myocardial tissue in the other three groups (except for the normal group) was obvious, but the PLA2G7 shRNA group showed certain improvement as compared with the blank group and the NC group (all P 0.05). Compared with the NC group, the PLA2G7 shRNA group had significantly decreased collagen volume fraction, myocardial fibrosis and area of thoracic aorta injury (all P 0.05). In conclusion, PLA2G7 silencing can improve the myocardial fibrosis in mice with coronary atherosclerosis, and PLA2G7 is expected to be a potential target for coronary atherosclerosis.

Long follow up is needed in prospective cohort study evaluation of plasma biomarkers for incident peripheral arterial disease (PAD) Middle-aged PAD-free individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (n = 5550; 1991–94) were followed prospectively for a median time of 23.4 years. The plasma biomarkers lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and mass, proneurotensin, and CRP, were studied in relation to incidence of PAD until December 31st, 2016. The diagnosis of PAD could be validated and confirmed in 98%. Cox regression was used to calculate hazard ratios (HR) per 1 standard deviation increment of each respective log transformed plasma biomarker. Cumulative incidence of PAD was 4.4% (men 5.9%, women 3.3%). Adjusting for age, gender, smoking, body mass index, hypertension, diabetes mellitus, Lp-PLA2 activity (HR 1.33; 95% CI 1.17–1.52), Lp-PLA2 mass (HR 1.20; 95% CI 1.05–1.37) and CRP (HR 1.55; 95% CI 1.36–1.76) remained independently associated with incident PAD. The plasma biomarkers Lp-PLA2 activity and mass, and CRP were markers of PAD risk, implying that they might be useful biomarkers for subclinical atherosclerosis and atherosclerotic disease.