脂蛋白相关磷脂酶A2:一种独立血管风险预测因子和治疗新靶点

脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2,Lp-PLA2)可快速水解氧化低密度脂蛋白和脂蛋白(a)中的氧化磷脂分子,生成可溶性促炎和促凋亡介质-溶血卵磷脂和氧化游离脂肪酸,刺激单核巨噬细胞系统聚集和激活,诱导细胞凋亡和破坏死亡细胞的清除,在动脉粥样硬化脂质坏死核心的发展中起重要作用.Lp-PLA2不仅是冠状动脉疾病和缺血性卒中的独立风险标志物,而且在动脉粥样硬化斑块进展中起重要作用.选择性Lp-PLA2抑制剂可减少坏死核心的发展,可能对动脉粥样斑块起稳定作用,同时可能代表着一种动脉粥样硬化的治疗新靶点.     

脂蛋白相关磷脂酶A2:一种独立血管风险预测因子和治疗新靶点

脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2,Lp-PLA2)可快速水解氧化低密度脂蛋白和脂蛋白(a)中的氧化磷脂分子,生成可溶性促炎和促凋亡介质-溶血卵磷脂和氧化游离脂肪酸,刺激单核巨噬细胞系统聚集和激活,诱导细胞凋亡和破坏死亡细胞的清除,在动脉粥样硬化脂质坏死核心的发展中起重要作用.Lp-PLA2不仅是冠状动脉疾病和缺血性卒中的独立风险标志物,而且在动脉粥样硬化斑块进展中起重要作用.选择性Lp-PLA2抑制剂可减少坏死核心的发展,可能对动脉粥样斑块起稳定作用,同时可能代表着一种动脉粥样硬化的治疗新靶点.     

脂蛋白相关磷脂酶A2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的研究进展

动脉粥样硬化（AS）是一种炎症性疾病,脂蛋白相关磷脂酶A2（lipoprotein-associated phospholipaseA2,Lp-PLA2）是心血管疾病中一种新的炎症酶,能水解氧化低密度脂蛋白（LDL）,产生溶血磷脂酰胆碱（lysophosphatidyl-choline,Lyso-PC）和氧化型游离脂肪酸（oxidizedfreefat-tyacids,ox-FA）,促进动脉粥样硬化的形成和发展,其与临床疾病的关系日益受到关注。     

脂蛋白相关性磷脂酶A2与缺血性心脑血管病

脂蛋白相关性磷脂酶A2（Lp-PLA2）是一种主要由巨噬细胞产生的反映血管炎症的特异性标记物,在低密度脂蛋白的氧化、促进动脉粥样硬化以及冠心病和卒中的形成等方面发挥重要作用。Lp-PLA2水平升高是预测冠心病和卒中风险的一种独立危险因素。     

脂蛋白相关性磷脂酶A2与冠心病的研究现状

脂蛋白相关性磷脂酶A2（1ipoprotein-associated phospholipase A2,Lp-PLA2）是近年来被广泛关注的与动脉粥样硬化和缺血性心脑血管病密切相关的磷脂酶家族分子,本文对Lp-PLA2的生物学特征及其与动脉粥样硬化形成与发展的相关研究进展做一综述.     

脂蛋白相关磷脂酶A2在缺血性卒中风险评估中的价值

脂蛋白相关磷脂酶A2是磷脂酶A2超家族的一个成员,由成熟的巨噬细胞和淋巴细胞合成和分泌,主要与低密度脂蛋白结合,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型游离脂肪酸,促进动脉粥样硬化形成,抑制脂蛋白相关磷脂酶A2活性可能有抗动脉粥样硬化的效应。在缺血性卒中的发病风险及预防性治疗上,脂蛋白相关磷脂酶A2是一个新的有待研究的因子,可能是缺血性卒中独立的预测因子及治疗靶     

脂蛋白相关磷脂酶A2在急性冠状动脉综合征中的研究进展

脂蛋白相关磷脂酶A2(Lp-PLA2)由炎症细胞产生,可以水解氧化型低密度脂蛋白(ox-LDL)产生炎症介质促进动脉粥样硬化。Lp-PLA2存在于不稳定斑块以及破裂斑块中,与急性冠状动脉综合征的发病机制有关。LpPLA2作为心血管事件的独立预测因子而受到广泛关注。Darapladib是一种特异性Lp-PLA2抑制剂,其Ⅲ期临床试验已完成,结果对于以粥样硬化炎症成份为新型治疗靶点的探索提出了新的挑战。     

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.     

慢性肾衰患者血浆脂蛋白相关磷脂酶A2与动脉粥样硬化的关系

目的研究慢性肾功能衰竭患者血浆脂蛋白相关磷脂酶A2(Lp-PLA2)水平与动脉粥样硬化的关系。方法选择慢性肾功能衰竭患者100例和健康对照40例采用酶联免疫吸附(ELISA)法测定血浆脂蛋白相关磷脂酶A2水平,超声技术检测颈动脉内膜中膜厚度和粥样硬化斑块。比较慢性肾衰患者与对照组血浆Lp-PLA2水平及慢性肾功能衰竭患者不同分组间Lp-PLA2水平,并对影响颈动脉颈动脉内膜中膜厚度的多因素进行逐步回归分析。结果慢性肾功能衰竭患者血浆Lp-PLA2水平明显高于健康对照组(232.16±59.36μg/L比129.47±29.72μg/L,P<0.01);透析者血浆Lp-PLA2水平明显高于未透析者(261.84±50.82μg/L比204.73±53.95μg/L,P<0.01);未透析者血浆Lp-PLA2水平与内生肌酐清除率呈负相关(r=-0.567,P<0.01)。有颈动脉粥样斑块者血浆Lp-PLA2水平明显高于无动脉粥样斑块者(281.33±39.72μg/L比188.46±35.02μg/L,P<0.01)。多因素逐步回归分析均显示血浆Lp-PLA2水平与颈动脉内膜中膜厚度呈正相关(β=0.735,P<...     

Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target

The development of atherosclerotic vascular disease is invariably linked to the formation of bioactive lipid mediators and accompanying vascular inflammation. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that is produced by inflammatory cells, co-travels with circulating low-density lipoprotein (LDL), and hydrolyzes oxidized phospholipids in LDL. Its biological role has been controversial with initial reports purporting atheroprotective effects of Lp-PLA2 thought to be a consequence of degrading platelet-activating factor and removing polar phospholipids in modified LDL. Recent studies, however, focused on pro-inflammatory role of Lp-PLA2 mediated by products of the Lp-PLA2 reaction (lysophosphatidylcholine and oxidized nonesterified fatty acids). These bioactive lipid mediators, which are generated in lesion-prone vasculature and to a lesser extent in the circulation (eg, in electronegative LDL), are known to elicit several inflammatory responses. The proinflammatory action of Lp-PLA2 is also supported by a number of epidemiology studies suggesting that the circulating level of the enzyme is an independent predictor of cardiovascular events, despite some attenuation of the effect by inclusion of LDL, the primary carrier of Lp-PLA2, in the analysis. These observations provide a rationale to explore whether inhibiting Lp-PLA2 activity and consequent interference with the formation of bioactive lipid mediators will abrogate inflammation associated with atherosclerosis, produce favorable changes in intermediate cardiovascular end points (eg, biomarkers, imaging, and endothelial function), and ultimately reduce cardiovascular events in high-risk patients.     

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.     

The role of lipoprotein-associated phospholipase A2 as a marker for atherosclerosis

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that belongs to the superfamily of phospholipase A2 enzymes. Although initial studies showed that Lp-PLA2 might be protective against atherosclerosis, emerging data seem to suggest that Lp-PLA2 may be proatherogenic, which is an effect thought to be mediated by lysophosphatidylcholine and oxidized nonesterified fatty acids, two mediators generated by Lp-PLA2. This article reviews the potential mechanisms by which Lp-PLA2 may participate in the pathogenesis of atherosclerosis and its clinical manifestations, namely, coronary artery disease and stroke.     

The molecular basis of vulnerable plaque: potential therapeutic role for immunomodulation

PURPOSE OF REVIEW: Atherosclerosis is a chronic inflammatory/immune disease involving multiple cell types including monocytes-macrophages, T-lymphocytes, mast cells, and endothelial cells. Through recent studies the role of the immune system on development of atherosclerosis and approaches to modulate this response are being elucidated. RECENT FINDINGS: The use of statins, PPARgamma agonists or lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors may play a role in reducing progression of atherosclerosis through immunomodulatory pathways. Oxidized LDL biases development toward the pro-inflammatory T-cell Th1 subset and recruits macrophages into the vascular wall. IFNgamma, produced by Th1 cells, inhibits PPARgamma effects. Lp-PLA2 levels correlate with an increased risk of recurrent ischemic events in patients presenting with acute coronary syndromes or myocardial infarction. SUMMARY: Recent research has shown that immune pathways play a major role in the development and progression of atherosclerosis. Commonly used medications, specifically statins and some PPARgamma agonists, have demonstrated anti-inflammatory/immune effects unrelated to their primary mode of action. Treatment of infectious agents has proven elusive in the clinical arena. Novel agents targeting immune and inflammatory pathways may prove beneficial in reducing progression and instability of the atherosclerotic plaque.