脂蛋白相关磷脂酶A_2在动脉粥样硬化中的作用

人血浆脂蛋白相关磷脂酶A2(Lp-PLA2)又称血小板活化因子乙酰水解酶(PAF-AH),主要由巨噬细胞合成和分泌。大部分Lp-PLA2与低密度脂蛋白结合,能水解灭活血小板活化因子,水解低密度脂蛋白上的氧化磷脂,生成溶血卵磷脂和氧化型游离脂肪酸,因此既有抗炎抗动脉粥样硬化,又有促炎促动脉粥样硬化的作用。近年来,越来越多的研究表明,Lp-PLA2具有促动脉粥样硬化作用,是心血管病的风险预测因子,可能成为心血管病新的治疗目标。     

脂蛋白相关磷脂酶A2与动脉粥样硬化性疾病

Lp-PLA2主要由巨噬细胞和淋巴细胞产生,是一个新的炎症标志,在动脉粥样硬化（AS）形成中起重要作用。许多研究表明,Lp-PLA2是冠心病危险的独立预测因子,抑制Lp-PLA2可能有抗AS的效应。     

脂蛋白相关磷脂酶A2与动脉粥样硬化疾病

近年来随着动脉粥样硬化疾病发病率的增加，对预测因子的研究成为当今的研究热点。脂蛋白相关磷脂酶A2主要由巨噬细胞和淋巴细胞产生，在以往的研究中，其既有促动脉粥样硬化的作用，又有抗动脉粥样硬化的作用。本文旨在对脂蛋白相关磷脂酶A2与动脉粥样硬化疾病的关系做一综述，并与高敏C反应蛋白对动脉硬化疾病预测价值进行比较，进而为进一步治疗提供思路。     

脂蛋白相关磷脂酶A2与动脉粥样硬化的关系

脂蛋白相关磷脂酶A2是一种炎性细胞分泌的能促使氧化磷脂水解的磷脂酶,血液循环中该酶的活性与年龄性别血脂水平及基因多态性等多种因素有关。脂蛋白相关磷脂酶A2主要以与脂蛋白结合的形式存在,它既能通过水解血小板活化因子、氧化磷脂等炎症介质达到抗动脉硬化的效果,又能通过水解氧化低密度脂蛋白分子中的氧化磷脂,使其产生促炎症物质溶血卵磷脂和氧化型游离脂肪酸而起到促动脉粥样硬化作用,因此与动脉粥样硬化的发生发展密切相关。脂蛋白相关磷脂酶A2的特异性抑制剂已被证实具有抗动脉硬化作用,脂蛋白相关磷脂酶A2正被作为动脉粥样硬化治疗的一个新靶点而受到广泛关注。     

脂蛋白相关磷脂酶A2与动脉粥样硬化

人血浆脂蛋白相关磷脂酶A2,又称血小板活化因子乙酰水解酶,由成熟的巨噬细胞和淋巴细胞合成和分泌,并受炎性介质的调节,主要与低密度脂蛋白结合,能水解血小板活化因子使之失去活性,又能水解低密度脂蛋白上的氧化卵磷脂,生成促炎物质溶血卵磷脂和氧化游离脂肪酸,因此既有抗炎抗动脉粥样硬化,又有促炎促动脉粥样硬化的作用。近来,越来越多研究表明脂蛋白相关磷脂酶A2具有促动脉粥样硬化作用,与心血管风险有关,可能成为冠心病新的治疗目标。     

脂蛋白相关磷脂酶A2与冠心病

脂蛋白相关磷脂酶A2(Lp-PLA2)是冠状动脉粥样硬化过程中一种重要的炎症标志物,大量的临床研究提示其对冠心病的进展有预测价值,也与斑块特征相关.Lp-PLA2特异性高,很少受其他炎症标志物影响,为临床筛选高风险人群提供新途径,也为冠心病的治疗提供新靶点.     

高水平脂蛋白相关磷脂酶A2与慢性肾脏病患者发生动脉粥样硬化相关

目的:分析慢性肾脏病(CKD)患者血浆脂蛋白相关磷脂酶A2(Lp-PLA2)的变化水平,探讨CKD患者发生动脉粥样硬化的危险因素。方法:采用横断面研究,选取2017年11月-2020年1月在东莞东华医院行血浆LpPLA2水平检测及颈动脉彩超检查的CKD 1-2期患者67例为CKD 1-2组,选取CKD 3-5期患者96例为CKD 3-5组,同时选取健康体检者61例为对照组,比较3组间血浆Lp-PLA2、肾小球滤过率(e GFR)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、载脂蛋白A(apo A)、载脂蛋白B(apo B)等指标的差异。运用logistic回归分析CKD患者发生动脉粥样硬化的危险因素。结果:CKD患者总胆固醇、HDL-C及apo A较对照组低,甘油三酯、LDL-C及apo B较对照组高,且CKD 3-5组与对照组间差异有统计学意义(P均0. 05)。CKD患者Lp-PLA2水平随CKD分期增加而升高,且较对照组高(P 0. 01)。CKD患者中,动脉粥样硬化患者具有较高的血浆Lp-PLA2水平(318. 39±18. 22 vs166. 15±15. 58,P 0. 01)。相关性分析显示Lp-PLA2与e GFR呈负相关(r=-0. 263,P=0. 001)。logistic回归分析显示Lp-PLA2及年龄是CKD患者动脉粥样硬化发生的独立危险因素,优势比分别为1. 007与1. 132。结论:CKD患者血浆Lp-PLA2水平升高,Lp-PLA2高水平是CKD患者发生动脉粥样硬化的独立危险因素。     

脂蛋白相关性磷脂酶A2与动脉粥样硬化关系的研究进展

血浆脂蛋白相关磷脂酶A2是由成熟的巨噬细胞和淋巴细胞合成和分泌的。大量的基础研究和临床试验表明,脂蛋白相关磷脂酶A2及其水解产物参与动脉粥样硬化的形成和发展,具有致动脉粥样硬化作用。脂蛋白相关磷脂酶A2抑制剂的研究及临床试验正在进行,且有望成为动脉粥样硬化治疗的新靶点。     

脂蛋白相关磷脂酶A2与缺血性卒中

人血浆脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipese A2,LP-PLA2)由成熟的巨噬细胞和淋巴细胞分泌,主要与低密度脂蛋白结合.近年来的研究表明,Lp-PLA2在动脉粥样硬化形成过程中起着重要作用,其基因多态性与缺血性卒中发生相关,其特异性抑制剂具有抗动脉粥样硬化作用.Lp-PLA2可能是缺血性卒中的新型独立危险因素和治疗靶标.     

脂蛋白相关磷脂酶A2与冠状动脉病变的关系

目的:对冠心病患者进行冠脉造影检查,并测定其血浆中脂蛋白相关磷脂酶A2(LP-PLA2)的水平,以探讨LP-PLA2与各型冠心病的病变支数、狭窄程度及斑块稳定程度的关系.方法:将入选收住本院的患者分四组,急性心肌梗死组51例,不稳定性心绞痛组48例,稳定性心绞痛组54例,冠脉造影正常者44例为对照组.入选冠心病患者的确诊依据世界卫生组织诊断标准和中华医学会的相关指南.所有患者均接受冠脉造影检查,同时采集血标本.用酶联免疫吸附(ELISA)法分别测定四组患者LP-PLA2浓度.所得数据使用SPSS统计软件处理,以P<0.05作为差异有统计学意义.结果:①在急性心肌梗死组、不稳定性心绞痛组、稳定性心绞痛组三组中的男性,高血压和吸烟史的比例较对照组高,稳定性心绞痛组和不稳定性心绞痛组高血压的发生率高于急性心肌梗死组,差异均有统计学意义(P均<0.05).②急性心肌梗死组高敏C反应蛋白,基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-1(T1MP-1)以及新喋呤均高于对照组、不稳定性心绞痛组及稳定性心绞痛组,差异均有统计学意义(P均＜0.05).③在稳定性心绞痛组和不稳定性心绞痛组中LP-PLA2水平较对照组高,差异有统计学意义(P<0.05),④各组内随着病变支数的增加,LP-PLA2的水平有逐步升高趋势,但差异无统计学意义.在病变支数相同时,各组之间进行比较差异无统计学意义(P均>0.05).将病变支数相同的患者合并结果显示:随着病变支数增加,LP-PLA2水平逐步升高,多支病变明显高于单支病变,差异有统计学意义(P<0.01).随着冠脉病变的支数增加,LP-PLA2水平及Gensini积分呈现逐步升高趋势,3支病变与单支病变差异有统计学意义.⑤LP-PLA2的水平与高敏C反应蛋白(R=0.02,P=0.82)、新喋呤(R=-0.11,P=0.14)、MMP-9(R=-0.15、P=0.40)以及TIMP-1(R=0.12,P=0.11)皆无相关性.结论:LP-PLA2的水平与冠脉的病变支数有着密切关系,可以在一定程度上反应冠脉的狭窄程度.LP-PLA2与冠脉粥样硬化和斑块稳定与否的关系,仍需进一步的实验评估.     

脂蛋白相关磷脂酶A2与颈动脉粥样硬化

脂蛋白相关磷脂酶A2(lipowotein-associated phospholipase A2, Lp-PLA2)是心血管疾病的一种新型生物学标志物.它在有症状颈动脉粥样硬化斑块中的表达高于无症状颈动脉粥样硬化斑块,其产物溶血磷脂胆碱与组织氧化应激和炎症有关.另外,Lp-PLA2在颈动脉粥样硬化斑块的不稳定性差异中起着较为独特的作用.     

脂蛋白相关磷脂酶A2与冠心病的相关性研究进展

目前中国居民冠心病的发病率和死亡率逐年增高。研究发现动脉粥样硬化是一个血管炎症反应的过程,传统的血清炎性标志物与冠心病的相关性缺乏特异性。新型血清炎性标志物血浆脂蛋白相关磷脂酶A2与冠心病的相关性尚未得到证实。现就脂蛋白相关磷脂酶A2与冠心病的相关性研究进展做一综述。     

Lipoprotein-associated phospholipase A2 prognostic role in atherosclerotic complications

Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the Lp-PLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.     

Lipoprotein-associated phospholipase A2 activity in obese adolescents with and without type 2 diabetes

Lipoprotein-associated phospholipase A2 (Lp-PLA2) was identified as a strong predictor for cardiovascular events. Furthermore, it is highly associated with obesity. The role of Lp-PLA2 in diabetes mellitus is controversial and analyses, especially in adolescents with type 2 diabetes (T2D), are missing. Therefore, we compared Lp-PLA2 activity between two obese age-, sex-, and BMI-matched cohorts of adolescents with and without T2D. Relationships between Lp-PLA2 activity and age, BMI, hemoglobin A1c, lipids, and adipokines were evaluated. Lp-PLA2 activity was analyzed in serum of 72 obese adolescents without T2D (mean age 15.2 ± 1.6 years) and in 65 obese adolescents with T2D (mean age 15.5 ± 1.8 years). Clinical data were obtained from the Diabetes-Patienten-Verlaufsdokumentation (DPV) registry. Surprisingly, obese adolescents with T2D had lower levels of Lp-PLA2 activity than obese children without T2D (160.2 ± 45.0 versus 180.9 ± 35.6 nmol/min/ml, p = 0.003), but this decrease could only be detected in male (158.8 ± 45.3 versus 190.8 ± 31.3 nmol/min/ml, p < 0.001) and not in female adolescents (162.1 ± 45.5 versus 167.7 ± 37.1 nmol/min/ml, p = 0.60). In multiple linear regression analysis, differences in Lp-PLA2 activity between cohorts remained large and significant (ß-coefficient: ?31.60, 95% confidence interval [?49.27;?13.93], p < 0.001). Furthermore, Lp-PLA2 activity was positively associated with BMI (ß-coefficient: 2.04 [0.68;3.40], p = 0.004) and negatively associated with the adipokines leptin (ß-coefficient: ?0.53 [?0.89;?0.17], p = 0.004) and adiponectin (ß-coefficient: ?3.06, [?5.63;?0.48], p = 0.02). Elevated mean glucose concentrations in adolescents with T2D were not associated with an increase but with a decrease of Lp-PLA2 activity. Hence, in young patients with T2D the Lp-PLA2 activity as a risk predictor for cardiovascular events needs further investigation.     

Lipoprotein-associated phospholipase A2 and risk of venous thrombosis in older adults

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme involved in inflammation and platelet function. Inherited deficiency and elevated levels are associated with atherosclerosis. Given potential common etiologies of atherosclerosis and venous thrombosis (VT), we hypothesized that low and high Lp-PLA2 would be associated with VT risk. Lp-PLA(2) mass and activity were measured in baseline samples of Cardiovascular Health Study participants (5,888 men and women age > or =65), excluding 354 reporting pre-baseline VT. The study endpoint was VT unrelated to cancer after 11.6 years follow-up. Hazard ratios were estimated using Cox proportional hazard models, adjusting for age, race, sex, and body-mass index. With 129 cases of VT, there was no association of Lp-PLA2 activity with risk. Adjusted hazard ratios were 1.19 (CI 0.62, 2.29) and 0.87 (CI 0.43, 1.76) for the lowest and highest decile, respectively, compared to the 10-25th percentile. Corresponding hazard ratios for Lp-PLA2 mass were 1.63 (CI 0.79, 3.34) and 1.33 (CI 0.61, 2.87). Results were robust to several definitions of low or high Lp-PLA2. While the association of Lp-PLA(2) levels with arterial disease events implies a role for this enzyme in atherogenesis, our findings suggest that it is not prothrombotic.