Increased activity of lipoprotein-associated phospholipase A2 in non-severe asthma

BackgroundGiven increased risk of cardiovascular events in asthma we hypothesized that lipoprotein-associated phospholipase A₂ (Lp-PLA₂), an enzyme involved in atherosclerosis, is associated with proinflammatory and prothrombotic blood alterations in this disease.MethodsIn 164 adult asthmatics (63 with severe asthma) we measured plasma Lp-PLA₂ activity using the PLAC test. We determined its relations to inflammation and prothrombotic blood alterations.ResultsIn asthma, Lp-PLA₂ was inversely related to the age (β = ?0.1 [?0.18 to ?0.02]) and was lower in women (n = 122 [74%], 205 [182–242] vs. 243 [203–262] nmol/min/ml, p = 0.001). Interestingly, Lp-PLA₂ correlated negatively with the asthma severity score (β = ?0.15 [?0.23 to ?0.07]), being 10.3% higher in those with non-severe (mild or moderate) asthma (n = 101, 62%) as compared to the severe disease subtype (224 [191–261] vs. 203 [181–229], p = 0.006 after adjustment for potential confounders). Lp-PLA₂ activity was positively related to the levels of low-density lipoprotein (β = 0.1 [0.02–0.18]), triglycerides (β = 0.11 [0.03–0.19]) and glucose (β = 0.1 [0.02–0.18]) and inversely to the tumor necrosis factor α (β = ?0.27 [?0.35 to ?0.2]), high sensitivity C-reactive protein (β = ?0.1 [?0.19 to ?0.02]) and fibrinogen (β = ?0.12 [?0.21 to ?0.03]), as well as prothrombin (β = ?0.16 [?0.24 to ?0.08]), and parameters describing thrombin generation potential, such as endogenous thrombin potential (β = ?0.14 [?0.21 to ?0.06]) and peak thrombin generated (β = ?0.2 [?0.28 to ?0.12]).ConclusionsElevated Lp-PLA₂ activity in non-severe asthmatics suggests increased atherosclerotic risk in this group. Lower Lp-PLA₂ activity accompanied by its inverse relationship to inflammatory or prothrombotic blood biomarkers observed in turn in severe asthmatics might be related to the pathogenesis of more severe asthma phenotype.     

脂蛋白相关性磷脂酶A2活性与冠心病的关系

目的:探讨血浆脂蛋白相关性磷脂酶A2(Lp-PLA2)活性与冠心病(CHD)传统危险因素的关系及与CHD发病的关系。方法:测定经冠状动脉造影证实的87例CHD患者和58例对照组的血浆Lp-PLA2活性、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平并进行比较;同时调查年龄、性别、高血压史、糖尿病史、高脂血症史及吸烟史等CHD危险因素,研究它们与Lp-PLA2活性的关系。结果:①CHD组血浆Lp-PLA2活性显著高于对照组(P<0.01)。②CHD组中男性并高脂血症者Lp-PLA2活性显著升高。血浆Lp-PLA2活性与TC、LDL-C呈正相关,与HDL-C呈负相关,而与年龄、高血压、糖尿病、吸烟、TG无关。③非条件Logistic多元回归分析显示,调整其他危险因素后,Lp-PLA2活性仍与CHD独立相关。结论:CHD患者血浆Lp-PLA2活性显著增高,与TC、LDL-C呈正相关,与HDL-C呈负相关,是CHD的独立危险因素。     

血浆脂蛋白相关性磷脂酶A2活性与颈动脉内中膜厚度的关系

目的探讨血浆脂蛋白相关性磷脂酶A2（1ipoprotein-associatedphosphalipaseA2,Lp-PLA2）活性与颈动脉内中膜厚度（carotidintima-mediathickness,CIMT）关系。方法收集168例患者,依据CIMT将患者分为A组（CIMT〉0．9mm）和B组（CIMT〈0．9mm）,检测两组血浆Lp-PLA2活性及其他指标,并分析Lp-PLA2活性及其他指标与CIMT的关系。结果（1）与B组相比,A组血浆Lp-PLA2活性明显升高,而血浆高密度脂蛋白胆固醇浓度则低于B组,差异有统计学意义（P〈0．05）;（2）Pearson或Spearman相关分析结果提示吸烟和Lp-PLA2活性与CIMT厚度呈正相关（r=0．665,P=0．168;r=0．815,P=0．001）,而高密度脂蛋白胆固醇则与CIMT呈负相关（r=-0．754,P=0．002）。结论对于仅合并吸烟及血浆低高密度脂蛋白胆固醇浓度的患者,其血浆Lp-PLA2活性升高与CIMT呈正相关。     

Role of lipoprotein-associated phospholipase A2 in atherosclerosis

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a biomarker that can be used to assess the risk for cardiovascular disease and events. In addition to being a useful marker of a risk factor, several studies suggest that Lp-PLA₂ has a pathophysiologic role in the atherosclerotic disease process. In this article, we review this aspect and its therapeutic implications.     

脂蛋白相关磷脂酶A2与原发性高血压的相关性

目的：研究原发性高血压（EH）患者血清脂蛋白相关磷脂酶A2（Lp-PLA2）水平的变化,探讨其变化在EH中的可能作用。方法：选择EH患者60例,其中高血压1级组患者20例,≥2级组20例,≥2级合并冠心病组20例。另选择健康体检者20例作为正常对照组。用酶联免疫吸附（ELISA）法检测定各组血清Lp-PLA2活性。结果：高血压≥2级合并冠心病组、≥2级组及1级组血清Lp-PLA2水平[（92.53±9.71）μg/L、（86.92±9.61）μg/L、（77.94±8.03）μg/L]均明显高于正常对照组[（71.30±5.99）μg/L],P〈0.05～〈0.01。多元线性逐步回归分析显示血清Lp-PLA2水平与收缩压、舒张压呈正相关（r=0.678,0.503,P均〈0.01）,亦与低密度脂蛋白胆固醇水平呈正相关（r=0.519,P〈0.01）。结论：血清脂蛋白相关磷脂酶A2水平与高血压的严重程度相关,可能参与高血压的发生、发展过程。     

脂蛋白相关磷脂酶A2与临床冠心病的关系

目的探讨冠心病患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)与冠状动脉(冠脉)炎症反应程度的关系。方法102例经冠脉造影证实的患者纳入冠心病(CHD)组,其中稳定型心绞痛(SAP)41例,不稳定型心绞痛(UAP)30例,急性心肌梗死(AMI)31例,对照组38例为冠脉造影正常的非冠心病者。所有对象造影前采集血标本以检测Lp-PLA2、C反应蛋白(CRP)和白细胞介素6(IL-6)。结果(1)冠心病组血清Lp-PLA2、CRP和IL-6均高于对照组(P<0.01);(2)AMI组与UAP组血清Lp-PLA2、CRP、IL-6比较差异无显著性(P>0.05),但均高于SAP组(P<0.01),在校正了心血管危险因素后差异仍有统计学意义;(3)经双变量相关性分析,血清Lp-PLA2水平与CRP、IL-6水平呈显著相关(r=0.722、0.665,P<0.01)。结论血清Lp-PLA2水平能反映冠脉炎症活动性状况,对冠心病的病情判断有一定价值。     

Correlation between lipoprotein-associated phospholipase A2 activity and its gene polymorphism in coronary heart disease

Objective To detect the mutation of A379,we developed a TaqMan fluorogenic probe based amplification refractory mutation system(TaqMan-ARMS) and investigate whether the A379V variant and activity of Lp-PLA2 were the risk factors for CAD. Methods According to the amplification refractory mutation system     

Moderate alcohol consumption and the gastrointestinal tract

BACKGROUND: A high alcohol intake is significantly associated with diseases of the gastrointestinal tract, but less is known about the effects of moderate consumption, specifically moderate average volume of alcohol consumption. METHODS: A systematic computer-assisted literature review was completed in order to review current scientific knowledge surrounding this topic. RESULTS: Moderate alcohol consumption is associated with a number of gastrointestinal health risks, including liver diseases, oropharyngeal cancer, esophageal cancer and pancreatitis but may play a positive role in gastritis and cholelithiasis. CONCLUSION: Moderate alcohol consumption may play a positive or negative role in disease etiology, but the overall conclusion is that moderate alcohol intake is not a high risk factor for many of the gastrointestinal diseases associated with high levels of consumption. The etiology of alcohol diseases is also linked to patterns of drinking, so this is an important area for future research in this area.     

Moderate alcohol consumption and coronary artery disease. A review

An inverse association between moderate alcohol consumption and coronary artery disease has been demonstrated in epidemiologic studies of diverse design. These include ecologic correlations, case-control, longitudinal and clinical studies. The consistency, strength and independence of the inverse relationship argues persuasively for a causal association. These data also suggest that both abstention and heavy alcohol use are associated with an increased risk for coronary artery disease. The effect of moderate alcohol consumption on lipoprotein and apolipoprotein levels is a biologically plausible and likely mechanism for this inverse association. Alcohol consumption elevates HDL cholesterol, although it is unclear whether the HDL subfractions HDL-2 and HDL-3 are beneficially altered. Recent evidence, however, suggests that the apolipoproteins may be more important indicators of coronary artery disease, and moderate alcohol consumption does beneficially alter these proteins. Alcohol may also affect coronary artery disease by other mechanisms, which may include fibrinolytic activity, coagulation, blood pressure, coronary vasoreactivity, and sociobehavioral factors.     

Effect of low-density lipoprotein apheresis on lipoprotein-associated phospholipase A2

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a proinflammatory participant in atherosclerosis and a potential biomarker for coronary heart disease. The effects of low-density lipoprotein (LDL) apheresis on Lp-PLA(2) levels were evaluated in 8 patients with cardiovascular disease. Each patient received 5 LDL apheresis treatments over a 3-month period. The mean direct LDL cholesterol level reduction was 60% (252 to 100 mg/dl). LDL apheresis acutely reduced Lp-PLA(2) by 21.4%. Over the course of treatment, Lp-PLA(2) levels were reduced by 29%. Chronic LDL apheresis significantly reduces Lp-PLA(2) independent of LDL cholesterol, which may be a potential mechanism by which LDL apheresis diminishes coronary heart disease risk.     

脂蛋白相关磷脂酶A2与冠状动脉斑块特征相关分析

目的探讨冠心病患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)与冠状动脉斑块特征的关系。方法回顾性分析2015年7月至2016年7月郑州大学第五附属医院和第一附属医院心血管内科行冠状动脉造影(CAG)检查和血管内超声(IVUS)检查的冠心病患者165例,根据IVUS结果分为稳定斑块组86例和易损斑块组79例,比较2组患者生化指标、IVUS指标和Lp-PLA2水平,分析Lp-PLA2水平与斑块特征的相关性。采用SPSS 17.0统计软件对数据进行分析。组间比较采用t检验或χ2检验,单因素分析采用Pearson直线相关分析,logistic回归分析影响斑块稳定的危险因素。结果易损斑块组相比稳定斑块组斑块负荷[(58.20±13.59)%vs(54.72±9.98)%]、血管重塑指数[(1.61±0.32)vs(1.13±0.26)]、斑块偏心指数[(1.58±0.15)vs(1.48±0.36)]和坏死组织[(25.1±9.9)%vs(12.3±7.5)%]以及钙化组织[(6.5±3.5)%vs(0.8±0.4)%]所占比例增高,纤维帽厚度[(0.60±0.27)vs(0.75±0.31)mm]、纤维化脂质组织[(17.0±5.6)%vs(20.2±6.1)%]和纤维组织[(59.9±7.5)%vs(62.2±7.1)%]比例降低,差异具有统计学意义(P0.05)。Lp-PLA2水平与斑块成分中坏死组织(r=0.514)、斑块负荷(r=0.395)、血管重塑指数(r=0.832)、斑块偏心指数(r=0.904)成正相关,与纤维帽厚度(r=-0.710)成负相关,差异具有统计学意义(P0.05)。斑块稳定性的危险因素为高血压(OR=6.82,95%CI2.16~21.46,P=0.01)、糖尿病(OR=2.65,95%CI 1.02~6.74,P=0.04)、吸烟史(OR=1.25,95%CI 1.06~1.62,P0.01)、低密度脂蛋白胆固醇(OR=1.36,95%CI 1.10~1.76,P0.01)、Lp-PLA2(OR=10.69,95%CI 1.72~66.91,P=0.001)。结论 Lp-PLA2水平可作为评估冠状动脉斑块是否稳定的敏感指标。     

Role of lipoprotein-associated phospholipase A2 in leukocyte activation and inflammatory responses

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an emerging cardiovascular risk marker. To explore the biologic role of Lp-PLA2 in atherosclerosis, we examined its expression and contribution to leukocyte activation under proatherogenic conditions. METHODS AND RESULTS: Following the induction of diabetes and hypercholesterolemia in a porcine model, a rapid increase in plasma Lp-PLA2 activity was observed at 1 month. This was accompanied by upregulated Lp-PLA2 mRNA expression by peripheral blood mononuclear cells (PBMC) at 3 months, and elevated Lp-PLA2 mRNA expression in coronary arteries at 6 months. These changes were paralleled by increased inflammatory responses by circulating PBMC (ICAM-1, IL-6), in coronary tissues (ICAM-1, VCAM-1), and the subsequent accumulation of inflammatory cells. In human PBMC, proinflammatory mediators augmented the synthesis and release of functional Lp-PLA2. Furthermore, lysophosphatidylcholine (lysoPC), a product of Lp-PLA2 activity, induced an increase in several inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in a concentration-dependent manner. In contrast, Lp-PLA2 inhibition (SB677116; 1 microM) abrogated the inflammatory response elicited by oxidized LDL. CONCLUSIONS: In an experimental model of diabetes and hypercholesterolemia, leukocyte activation was associated with augmented Lp-PLA2 expression. In vitro, Lp-PLA2 activity mediated leukocyte activation and inflammatory responses, whereas Lp-PLA2 inhibition abolished inflammatory responses induced by oxidized LDL. Collectively, these observations support a proatherogenic role for Lp-PLA2.     

Apo E4 and lipoprotein-associated phospholipase A2 synergistically increase cardiovascular risk

ObjectiveApolipoprotein E (apoE) has been implicated as conveying increased risk for coronary artery disease (CAD). Previous studies suggest a role of apoE as a modulator of immune response and inflammatory properties. We hypothesized that the presence of apo E4 is associated with an increased inflammatory burden in subjects with CAD as compared to subjects without CAD.MethodsApoE genotypes, systemic (C-reactive protein [CRP], fibrinogen, serum amyloid-A [SAA]) and vascular inflammatory markers (Lipoprotein-associated phospholipase A₂ [Lp-PLA₂] and pentraxin-3 [PTX-3]) were assessed in 324 Caucasians and 208 African Americans, undergoing coronary angiography.ResultsFor both ethnic groups, Lp-PLA₂ index, an integrated measure of Lp-PLA₂ mass and activity, increased significantly and stepwise across apoE isoforms (P = 0.009 and P = 0.026 for African Americans and Caucasians respectively). No differences were found for other inflammatory markers tested (CRP, fibrinogen, SAA and PTX-3). For the top cardiovascular score tertile, apo E4 carriers had a significantly higher level of Lp-PLA₂ index in both ethnic groups (P = 0.027 and P = 0.010, respectively).ConclusionThe presence of the apo E4 isoform was associated with a higher level of Lp-PLA₂ index, a marker of vascular inflammation. Our results suggest that genetic variation at the apoE locus may impact cardiovascular disease risk through enhanced vascular inflammation.     

高血浆高半胱氨酸和脂蛋白相关磷脂酶A2水平与痴呆的相关性

目的 探讨血浆高半胱氨酸(homocysteine, Hcy)和脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2, Lp-PLA2)水平与痴呆的相关性.方法 回顾性纳入住院的痴呆患者,根据Hachinski缺血量表分为血管性痴呆(vascular dementia, VaD)组、混合性痴呆(mixed dementia, MD)组和阿尔茨海默病(Alzheimer''s disease, AD)组,同时根据简易精神状态检查量表将痴呆严重程度分为轻度、中度和重度.另选同时期住院的非痴呆患者作为对照组.比较各组人口统计学、血管危险因素以及血浆Hcy和Lp-PLA2水平.应用logistic回归分析确定血浆Hcy和Lp-PLA2水平与痴呆风险和严重程度的独立相关性.结果 共纳入125例痴呆患者,VaD组52例(41.6%),MD组21例(16.8%),AD组52例(41.6%);轻度组49例(39.2%),中度组51例(40.8%),重度组25例(20%).40例非痴呆患者被纳入作为对照组.VaD组、MD组和AD组血浆Hcy及Lp-PLA2水平均显著高于对照组(P均<0.001).多变量logistic回归分析显示,高龄[优势比(odds ratio, OR)1.12,95%可信区间(confidence interval, CI)1.03~1.21;P=0.010]、高血浆Hcy水平(OR 1.44,95% CI 1.21~1.71;P<0.001)、高Lp-PLA2水平(OR 1.01,95% CI 1.00~1.02;P=0.006)和既往卒中史(OR 4.29,95% CI 1.50~12.36;P=0.007)是痴呆的独立危险因素;高Hcy水平(OR 1.48,95% CI 1.21~1.82;P<0.001)、高Lp-PLA2水平(OR 1.01,95% CI 1.00~1.03;P=0.002)和既往卒中史(OR 152.78,95% CI 20.41~999.97;P<0.001)是VaD的独立危险因素;高龄(OR 1.10,95% CI 1.02~1.17;P=0.008)和高Hcy水平(OR 1.41,95% CI 1.25~1.58;P<0.001)是重度痴呆的独立危险因素.结论 血浆Hcy和Lp-PLA2水平升高与痴呆相关,降低血浆Hcy和Lp-PLA2水平可能对治疗和预防痴呆有益.     

青年人急性心肌梗死与血浆脂蛋白相关磷脂酶A2水平的相关性研究

目的 探讨青年急性心肌梗死(AMI)患者冠脉病变与血浆脂蛋白相关磷脂酶A2 (Lp-PLA2)水平的关系.方法 选择31例青年AMI患者为研究对象(AMI组),28例冠脉造影正常的青年人为对照组(NC组),比较两组临床资料、冠脉病变特点,使用酶联免疫吸附法(ELISA)检测两组患者血浆Lp-PLA2水平.结果 青年AMI组吸烟、高胆固醇血症、冠心病家族史比例显著高于NC组(P＜0.01);AMI组血浆Lp-PLA2水平较NC组显著增高(P＜0.01),且血浆Lp-PLA2水平与冠脉Gensini积分呈正相关(r=0.726,P＜0.01).结论 血浆Lp-PLA2水平可能反映青年AMI患者冠脉病变程度.     

血清脂蛋白相关磷脂酶A_2水平与冠心病关系

目的探讨冠心病患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)的水平与冠状动脉粥样斑块稳定性和冠状动脉病变程度的关系及临床意义。方法144例患者根据冠状动脉造影结果分为冠状动脉粥样硬化性心脏病(冠心病,n=96)组和对照组(n=48),冠心病患者再根据临床症状、病变支数、Gensini积分分组,ELISA方法检测受试者Lp-PLA2水平,进行对比分析。结果冠心病患者血清Lp-PLA2水平显著高于对照组(P0.01);急性心肌梗死(AMI)组Lp-PLA2水平显著高于稳定型心绞痛(SAP)组、不稳定型心绞痛(UAP)组(P均0.01);不同病变支数组和Gensini积分组之间Lp-PLA2水平有显著性差异(P均0.01);冠心病Logistic回归分析结果示Lp-PLA2与冠心病独立相关,优势比为1.028～1.068。冠状动脉Gensini积分的多元逐步回归分析显示Lp-PLA2与冠脉积分独立相关,(P0.01)。结论Lp-PLA2是冠心病的独立危险因素之一,血清Lp-PLA2水平能反映冠状动脉粥样斑块的稳定性及冠状动脉病变的严重程度。     

The correlation between lipoprotein-associated phospholipase A2 and severity of coronary artery diseases

正Objective To investigate the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and the severity of coronary artery diseases.Meth-o dsA case-control study was conducted to select 231 patients with positive coronary angiography results in Beijing Huaxin Hospital. They were divided into two groups(untreated goup:147 cases; the medication group:84