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Objective:To investigate the predictive values of serum hypersensitive C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A 2 (Lp-PLA 2) for early neurological deterioration (END) and parenchymal hematoma (PH)-type 2 hemorrhagic transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke. Methods:Patients with acute ischemic stroke treated with intravenous thrombolysis in the Department of Neurology, Nanjing First Hospital, Nanjing Medical University from January 2018 to January 2021 were enrolled retrospectively. END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale (NIHSS) score at 24 h after thrombolysis compared with the baseline. PH-2 type HT was defined as parenchymal hematoma with obvious space occupying effect or hemorrhage at the distant site of infarct. Multivariate logistic regression analysis was used to determine the independent influencing factors of END and PH-2 type HT. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of hs-CRP and Lp-PLA 2 levels for END and PH-2 type HT. Results:A total of 804 patients with acute ischemic stroke treated with intravenous thrombolysis were included, of which 63 (7.8%) developed END within 24 h after intravenous thrombolysis; 41 (5.1%) developed HT, of which 38 were PH-2 type HT. Univariate analysis showed that the levels of serum hs-CRP and Lp-PLA 2 in the END group were significantly higher than those in the non-END group (all P<0.05), and the levels of serum hs-CRP and Lp-PLA 2 in the PH-2 HT group were significantly higher than those in the non-PH-2 HT group ( P<0.05). Multivariate logistic analysis showed that hs-CRP (odds ratio [ OR] 1.017, 95% confidence interval [ CI] 1.001-1.034; P=0.043) and Lp-PLA 2 ( OR 1.002, 95% CI 1.000-1.003; P=0.020) were the independent risk factors for END after intravenous thrombolysis. In addition, hs-CRP ( OR 1.019, 95% CI 1.002-1.036; P=0.027) and Lp-PLA 2 ( OR 1.002, 95% CI 1.000-1.003; P=0.018) were also the independent risk factors for PH-2 HT after intravenous thrombolysis. The ROC curve analysis showed that the areas under the curve of hs-CRP and Lp-PLA 2 for predicting END were 0.675 (95% CI 0.609-0.741; P<0.001) and 0.606 (95% CI 0.528-0.683; P=0.005) respectively, and the areas under the curve for predicting PH-2 HT were 0.641 (95% CI 0.545-0.737; P=0.003) and 0.600 (95% CI 0.500-0.699; P= 0.051) respectively. Conclusion:Higher baseline serum hs-CRP and Lp-PLA 2 are the independent predictors of END and PH-2 type HT after intravenous thrombolysis in patients with acute ischemic stroke.
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Objective To investigate the auxiliary diagnostic value of combined detection serum lipoprotein-associated phospholipase A2 (LP-PLA2) and small and dense low-density lipoprotein (sd-LDL) in atherosclerosis.Methods The subjects were divided into experimental group and control group by random block design from May 2017 to January 2018,in the First Affiliated Yijishan Hospital of Anhui Wannan Medical College.The experimental group selected 125 AS patients with clinical diagnosis and confirmed by angiography,and 55 healthy subjects were chosen as the normal control group at the same time.Serum samples were collected within 24 hours after admission,and the level of LP-PLA2,sdLDL-C,low density lipoprotein cholesterol (LDL-C),triglyceride (TG),total cholesterol (TC) and high-sensitive C reactive protein (hs-CRP) were unified detection.The t test,single factor variance analysis and Mann-Whitney U and multivariate logistic regression analysis were used to analyze the data.Results LP-PLA2,sd-LDL,LDL,TC,TG and hs-CRP of the AS group were all higher than those of the healthy control group (Z=5.279,6.663,6.012,5.863,5.508 and 2.845,respectively,P＜0.05).Logistic regression analysis showed that serum LP-PLA2,sd-LDL and hs-CRP level was an independent risk factor for predicting atherosclerosis (OR=1.008,P=0.003;OR=8.282,P=0.012;OR=1.158,P=0.009).The sensitivity of LP-PLA2,sd-LDL,LDL-C,TC,TG,hs-CRP to AS was detected separately (57.6％,73.6％,85.6％,83.2％,76.8％,80.0％),and the specificity was (89.1％,78.2％,67.3％,69.1％,74.5％,52.7％).The ROC curve showed that the diagnostic efficacy of LP-PLA2 and sd-LDL combined detection was 0.854,higher than sd-LDL,LDL-C,TC,TG,LP-PLA2 and hs-CRP (0.811,0.782,0.775,0.758,0.747 and 0.633,respectively).In addition,the levels of both increased with the aggravation of arteriosclerotic lesion(x2=7.954,P=0.019;x2=11.44,P=0.003).The levels of LP-PLA2 and sd-LDL in patients with AS were not significantly different between different lesions (x2=8.042,P=0.09;x2=5.952,P=0.203).There was no significant difference between serum LP-PLA2 and sd-LDL level and sex,age,smoking,hypertension and diabetes (Z1=0.398,0.719,0.619,0.098 and 1.338 respectively,Z2=0.942,0.027,0.894,0.375,0.783,respectively,both P1 and P2 were＞0.05).Conclusions sd-LDL combined with LP-PLA2 has high sensitivity and specificity in the prediction of AS,which makes up for the deficiency of individual detection;sd-LDL and LP-PLA2 serum level has nothing to do with the lesion and has a positive correlation with the degree of lesions.It is not easily affected by other risk factors and can be used as a risk factor for predicting the occurrence of AS.
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Lipoprotein ( a ) [ Lp ( a ) ] is considered a causal risk factor for the formation and development of atherosclerosis ( AS).High plasma levels of Lp ( a) is recognized as a predictor of coronary heart disease. However, the pathogenic mechanisms of Lp ( a ) are still unknown. Recent studies demonstrated that a key role in the proatherogenic effects of Lp ( a ) may be linked to its oxidized phospholipids ( OxPL) content.Lipoprotein-associated phospholipase A 2 ( Lp-PLA2 ) is another important factor in Lp( a) functionality.OxPL are hydrolyzed by Lp-PLA2 into lysophosphatidylcholine ( lyso-PC) and oxidized free fatty acid(OxFFA), which are important inflammatory factors on promoting the occurrence and development of AS.The present review article describes Lp-PLA2 hydrolyzing OxPL associated with Lp (a). The process induces inflammatory factors , which promote development of AS .OxPL and Lp-PLA2 can be used as new targets of cardiovascular diseases , which have clinical application value to predict potential cardiovascular diseases .
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Objective To evaluate the analytical performance of four lipoprotein associated phospholipase A2(Lp-PLA2)activity reagents on Beckman AU5800 automatic biochemical analyzer. Methods The remaining serum samples of 214 patients and 140 apparently healthy individuals were collected from March to July 2017 in Peking Union Medical College Hospital.These samples were used for method comparison and reference interval evaluation.According to the guidelines of EP15-A,EP6-A,EP-17 and EP7-P from Clinical and Laboratory Standards Institute(CLSI)standards,the precision, linearity, sensitivity and common interferences(e.g free bilirubin, conjunct bilirubin, hemoglobin and chyle)were assessed.According to EP9-A2,method comparisons of differents regents(Evermed,DiaSys,Hengxiao and Zhongyuan were labeled as A,B,C and D,respectively)were conducted and the differences were estimated at medical decision levels(328U/L,391U/L and 485U/L).Results The precision of four reagents were acceptable.The repeatability(CV%)of A to D were 0.5%-1.7%, 0.7%-3.0%, 0.9%-2.0% and 0.5%-3.3%,respectively.The reproducibility(CV%)were 0.7%-2.9%, 1.4%-3.2%, 1.3%-1.9%and 0.8%-4.1%,respectively.Both of those achievedlaboratory defined quality objective(<5%).The linearity of A to D were 44 -1 992 U/L,39 -1 798 U/L,13 -540 U/L and 75-1 717U/L,respectively.The regression coefficient R2 was between 0.997 and 1.000, and the correlation coefficient(r)was between 0.998 and 1.000.The interference of chyle were acceptable among these four reagents andmet the manufacturer′s requirementsor clinical needs.In a low level of Lp-PLA2,bilirubin had an obvious interferenceonreagent C;B and C were negatively affected when the hemoglobin was 4.5 g/L; and D was positively affected when the hemoglobin was 2.45 g/L.The regression coefficients R2 of A,C,D compared with B were between 0.978 and 0.995,and the correlation coefficients(r)were between 0.989 and 0.998. The expected differences at medical decision levels ranged from -240 U/L to 113 U/L.For A to D,the Lp-PLA2 activity results of 131(93.6%), 140(100%), 82(58.6%), and 128(91.4%)cases were analysed within the manufacturer′s claimed reference intervals.Conclusion The precision and linearity of the four Lp-PLA2 activity detection reagents used in automatic biochemical analyzer are good, but the anti-interference ability needs to be improved.
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Objective To study the effect of recombinant human platelet activating factor acetylhydrolase (rPAF-AH) on candidate plasticity-related gene 15 (CPG15) expression in focal cerebral ischemia rats.Methods Forty-five SD rats were randomly divided into sham operation group,saline group and rPAF-AH group (15 in each group).A middle cerebral artery occlusion model of rats was established for the latter two groups.Each group was divided into 2 d group,7 d group,14 d group.Five rats in each of 2 d group,7 d group,14 d group were used in experiment.The total protein was extracted from coronary sections using homogenate.CPG15 protein expression was detected by Western blot.Results The CPG15 protein expression level was significantly higher in saline group and rPAF-AH group than in sham operation group on days 2,7,14 and reached its peak on day 7,and in rPAF-AH group than in saline group on day 7 (1.48±0.04 vs 1.12±0.05,P＜0.01).Conclusion PAF-AH plays a positive role in neuroplasticity of cerebral ischemia by upregulating the CPG-15 expression in focal cerebral ischemia rats.
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ObjectiveTo investigate the associations of plasma homocysteine (Hcy) and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels with dementia.MethodsThe patients with dementia admitted to hospital were enrolled retrospectively.They were divided into a vascular dementia (VaD) group, a mixed dementia (MD) group, and an Alzheimer's disease (AD) group according to the Hachinski Ischemic Score, and the dementia severity was further divided into a mild group, a moderate group and a severe group according to the Mini-Mental State Examination.The non-demented patients hospitalized during the same period were selected as controls.The demographics, vascular risk factors, and plasma Hcy and Lp-PLA2 levels in each group were compared.Logistic regression analysis was used to determine the independent associations of the plasma Hcy and Lp-PLA2 levels with the risk of dementia and severity.ResultsA total of 125 patients with dementia were enrolled, including 52 (41.6%) in the VaD group, 21 (16.8%) in the MD group, and 53 (41.6%) in the AD group.There were 49 patients (39.2%) in the mild group, 51 (40.8%) in the moderate group, and 25 (20%) in the severe group.A total of 40 non-demented patients were enrolled as control group.The plasma Hcy and Lp-PLA2 levels in VaD, MD and AD groups were significantly higher than those in the control group (all P<0.001).Multivariable logistic regression analysis showed that the advanced age (odds ratio[OR] 1.12, 95% confidence interval [CI] 1.03-1.21;P=0.010), high plasma Hcy level (OR 1.44, 95% CI 1.21-1.71;P<0.001), high Lp-PLA2 level (OR 1.01, 95% CI 1.00-1.02;P=0.006), and previous stroke (OR 4.29, 95% CI 1.50-12.36;P=0.007) were the independent risk factors for dementia;high Hcy level (OR 1.48, 95% CI 1.21-1.82;P<0.001, high Lp-PLA2 level (OR 1.01, 95% CI 1.00-1.03;P=0.002), and previous stroke (OR 152.78, 95% CI 20.41-999.97;P<0.001) were the independent risk factors for VaD;advanced age (OR 1.10, 95% CI 1.02-1.17;P=0.008) and high Hcy level (OR 1.41, 95% CI 1.25-1.58;P<0.001) were the independent risk factor for severe dementia.ConclusionsThe increased plasma Hcy and Lp-PLA2 levels are associated with dementia.Reducing the plasma Hcy and Lp-PLA2 levels may be beneficial to the treatment and prevention of dementia.
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Objective To study the correlations among the lipoprotein associated phospholipase A2 (Lp‐PLA2) ,hypersensitive C‐reactive protein(hs‐CRP)and D‐dimmer in patients with the coronary heart disease .Methods 260 cases of patients with coronary heart disease(CHD) were enrolled in the study as observation group and 260 healthy people from the physical examinations were recruited as control group .The concentrations of Lp‐PLA2 ,hs‐CRP ,D‐dimer and other biochemical indicators in blood sera of the two groups were detected ,using the Spearman correlation analysis to test the relationship between those indicators .Results The Lp‐PLA2 ,hs‐CRP ,D‐dimer levels of the observation group were obviously higher than those of control group .The Lp‐PLA2 level of the observation group was positively correlated with the cardiac function index(r=0 .873 ,P<0 .05) .hs‐CRP was positively cor‐related with cardiac function index(r=0 .782 ,P<0 .05) .D‐dimmer was positively correlated with the functional grades of heart(r=0 .674 ,P<0 .05) .Conclusion Lp‐PLA2 ,hs‐CRP and D‐dimer could be important indicators for the detection of coronary heart disease .
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Objective To investigate the correlation between lipoprotein-associated phospholipase A2 (Lp-PLA2) gene R92H polymorphism and ischemic stroke and its subtype in a Chinese Han population of Shandong province. Methods A total of 386 patients w ith first-ever ischemic stroke and 368 healthy controls in China Shandong region w ere enrol ed. According to the TOAST criteria, the patients w ere further divided into large artery atherosclerosis (LAA) and smal artery occlusion (SAO). Enzyme linked immunosorbent assay w as used to detect the serum Lp-PLA2 level. Polymerase chain reaction and directly sequencing w ere used to detect R92H gene polymorphism. Results The serum Lp-PLA2 levels in the ischemic stroke group, LAA group and SAO group w ere higher than that in the control group, and there w ere significant differences (al P<0.01). The distribution frequencies of GA (P=0.006), AA (P=0.020), AA+AG (P=0.009), and A al ele (P=0.001) in the ischemic stroke group w ere significant higher than those in the control group. There w ere also significant differences in distribution frequencies of GA+AA genotype (P=0.007) and A al ele (P<0.001) betw een the LAA group and the control group, w hile the SAO group w as not the case. Multivariate logistic regression analysis showed that GA+ AA genotype (odds ratio [OR] 1.43, 95%confidence interval [CI] 1.02-2.00; P=0.029), GA genotype (OR 1.42, 95%CI 1.01-2.00; P=0.037), and A alele (OR 1.44, 95%CI 1.11-2.18; P=0.028) were the independent risk factors for ischemic stroke. GA+AA genotype (OR 1.73, 95%CI 1.18-2.55; P<0.001) and GA genotype (OR 1.67, 95%CI 1.13-2.48; P<0.001) w ere the independent risk factors for LAA, and they w ere not significantly independent correlated w ith SAO. Conclusions The serum Lp-PLA2 levels increased in patients w ith ischemic stroke, and they increased most significantly in the LAA group. The R92H gene polymorphism might be associated w ith the susceptibility of ischemic stroke in a Chinese Han population of Shandong province.
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Introducción. El dengue grave se caracteriza por el aumento de la permeabilidad vascular inducida por citocinas y mediadores químicos; uno de estos es el factor activador de plaquetas. La acetilhidrolasa del factor activador de plaquetas es la enzima responsable de su degradación, y su deficiencia o aumento se ha relacionado con varias enfermedades. Sin embargo, su papel en la infección por dengue es poco conocido, como tampoco se sabe si existe diferente actividad según el grupo étnico. Objetivo. Comparar la actividad en suero de la acetilhidrolasa del factor activador de plaquetas en dos grupos étnicos con infección por el virus del dengue. Materiales y métodos. Se llevó a cabo un estudio descriptivo, longitudinal, prospectivo, en dos departamentos de Colombia, Antioquia y Chocó. A 43 pacientes mestizos y a 33 pacientes afrodescendientes con diagnóstico de dengue, se les tomó una muestra de suero por cinco días consecutivos en la fase aguda y una muestra en la de convalecencia. Resultados. Se observó mayor frecuencia de casos de dengue hemorrágico en los pacientes mestizos que en los afrodescendientes (23,3 % Vs. 12,1 %, p=0,248). La actividad sérica de la acetilhidrolasa del factor activador de plaquetas (mediana, percentil 25 y percentil 75) fue más elevada en afrodescendientes que en mestizos (0,89 (0,72-1,10) Vs. 0,76 (0-1,03), p=0,000). Este comportamiento se conserva en el dengue clásico (0,89 (0,73-1,10) Vs. 0,73 (0-1,05), p=0,000) y en el hemorrágico (0,88 (0,69-1,12) Vs. 0,83 (0,71-1,08), p=0,893). Conclusiones. Se encontró mayor producción de acetilhidrolasa del factor activador de plaquetas en los pacientes afrodescendientes. Sin embargo, es necesario hacer estudios de polimorfismos de esta enzima que permitan obtener resultados concluyentes.
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Adolescent , Female , Humans , Male , Young Adult , /blood , Dengue/blood , Black People , Dengue/enzymology , Indians, South American , Longitudinal Studies , Prospective StudiesABSTRACT
Objective To investigate the relationship between activity of plasma platelet-activating factor acetylhydrolase (PAF-AH)and insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS). Methods From Oct. 2006 to Jan. 2008, 105 PCOS patients undergoing treatment in Department of Obstetrics and Gynecology of Second Hospital affiliated to West China University were enrolled in the study, among 53 cases with homeostatic model assessment IR (HOMA-IR) exceed or equal 2.77 as IR-PCOS group and 52 cases with HOMA-IR less than 2.77 as non IR-PCOS group. In the mean time, 53 infertile women due to fallopian tube or husband factors were chosen as control group. Plasma PAF-AH activity, high-density lipoprotein-associated PAF-AH (H-PAF-AH) activity, low-density lipoprotein-associated PAF-AH (L-PAF-AH) activity, the ratio of L-PAF-AH to H-PAF-AH activity were measured and compared among three groups. The method of Pearson correlation analysis and stepwise multiple regression analysis were used to study the relationship between the ratio of L-PAF-AH to H-PAF-AH activities and hormonal and metabolic parameters. Results (1) Plasma PAF-AH activity [ (0.055±0.012) mmol· L~(-1)·min~(-1)], L-PAF-AH activity [(0.052±0.012) mmol·L~(-1)·min~(-1)], and the ratio of L-PAF-AH to H-PAF-AH activity (23±6) in the IR-PCOS group were significantly higher than those at control group [(0.050±0.009) mmol·L~(-1) ·min~(-1), (0.047±0.009) mmol·L~(-1)·min~(-1) and (18±4)] and non-IR-PCOS group [(0.050±0.0012) mmol·L~(-1) ·min~(-1), (0.048±0.012) mmol·L~(-1)·min~(-1) and (18± 5 ), P <0.05 ]. The ratio of L-PAF-AH to H-PAF-AH activities at IR-PCOS group was also significantly higher than those at Non IR-PCOS and control group after correction for body mass index (P<0.01). (2) Pearson correlation analysis showed that the ratio of L-PAF-AH to H-PAF-AH in PCOS patients was positively correlated with atherogenic index, age, body mass index, waist-to-hip ratio, HOMA-IR, triglyceride levels, fasting insulin levels, fasting glucose levels, low density lipoprotein cholesterol and total cholesterol (r=0.644, 0.247, 0.296, 0.212, 0.356, 0.587, 0.377, 0.375, 0.292 and 0.199, respectively, P<0.05), and negatively correlated with high density lipoprotein cholesterol (r=-0.510, P<0.05). The multiple stepwise regression analysis showed that atherogenic index and triglyceride were significant variables for the ratio of L-PAF-AH to H-PAF-AH activity (standardized coefficient, β=0.515 and 0.201, respectively, P<0.05). Conclusion The elvated L-PAF-AH activity may be associated with IR in PCOS patients, and the increased ratio of L-PAF-AH to H-PAF-AH activities may be a potential marker of inflammation in the patients.
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Objective To investigate the plasma PAF-AH level in initialed type 1 diabetes patients and the association between the PAF-AH gene polymorphism and type 1 diabetes mellitus. Methods155 initialed type 1 diabetes patients and 138 controls were selected in this study. Plasma PAF-AH was determined by PAF-AH Assay kit, and the PAE-AH gene G994t genotypes were detected by PCR. ResultsThe activity of plasma PAF-AH in the patients with type 1 diabetes was significantly lower than that in the controls[ (20.64 ± 6.23)nmol/(min · ml) vs (28.56 ± 4. 11)nmol/(min · ml), P ＜0.05). Compared with control group, the frequencies of the GT genotype on G994T polymorphism between type 1 diabetes patients and controls were not significantly different(8.4％ vs 7. 2％, P ＞0. 05). ConclusionThe activity of plasma PAF-AH in the patients with type 1 diabetes was significantly lower than controls. The G994T polymorphism of PAF-AH gene was not related to type 1 diabetes mellitus.
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Lipoprotein-associated phospholipase A2(Lp-PLA2) can rapidly hydrolize and oxidize the oxidized phosphatidylcholine molecules produced in low density lipoprotein and atherogenic lipoprotein (a),generating the soluble proinflammatory and proapoptotic mediatorslyso-phosphatidylcholine and oxidized free fatty acids.It stimulates aggregation and activation of monocyte-macrophage system and induces apoptosis and damages the removal of dead cells.It plays an important role in the development of lipid necrotic core of atherosclerosis.Lp-PLA2 is not an independent risk marker of coronary artery disease and ischemic stroke,but also plays an important role in the development of atherosclerotic plaques.Selective Lp-PLA2 inhibitor reduces the development of necrotic cores.It may play a role in the stabilization of atherosclerotic plaques.At the same time,it may represent a novel target for the treatment of atherosclerosis.
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Objective To investigate the plasma PAF-AH level in type 1 diabetes patients and the association between the PAF-AH gene polymorphism and type 1 diabetes mellitus. Methods Plasma PAF-AH in115 type 1 diabetes patients and 106 controls were determined by PAF-AH assay kit, and PAF-AH gene G275A genotypes were detected by PCR-RLFP. Results The activity of plasma PAF-AH in the patients with type 1 diabetes was significantly lower than that in the controls. Compared with control group, the frequencies of the GA genotype on G275A polymorphism were significantly higher than that in T1DM group. Conclusion The activity of plasma PAF-AH in the patients with type 1 diabetes was significantly lower than that in normal controls. The G275A polymorphism of PAF-AH gene might be related to type 1 diabetes mellitus.
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Objective To investigate the relationship between a mutation in the platelet-activating factor (PAF) acetylhydrolase gene (Arg92→His) and psoriasis. Methods Genomic DNA was analyzed in 47 patients with psoriasis and 52 healthy controls via polymerase chain reaction and restriction fragment length polymorphism. Results The frequency of the mutation in the PAF acetylhydrolase gene (Arg92→His) was significantly higher in patients with psoriasis than that in the controls (P