We conducted a metaanalysis to determine whether elevated lppla2 is a risk factor for stroke. Endothelial dysfunction in children with obstructive sleep. Increased levels of lipoproteinassociated phospholipase a 2 are associated with atherosclerosis, and may contribute to cardiac disease. By continuing to use our website, you are agreeing to our use of cookies. However, the molecular effects of lppla2 on atherosclerosis have not been fully investigated. Lppla2 then breaks the oxidized phosphatidylcholine into two bioactive compounds, lysophosphatidylcholine and oxidized nonesterified free. The anticipated presence of low circulating concentrations. Ldl particles are heterogeneous, differing in size and density. The starting fragment hit was discovered through an xray fragment screen and showed no activity in the bioassay ic 50 1 mm. Effect of darapladib treatment on endarterectomy carotid. Lipoproteinassociated phospholipase a2 and its association with cardiovascular outcomes in patients with acute coronary syndromes in the prove ittimi 22 pravastatin or atorvastatin evaluation and infection therapythrombolysis in myocardial infarction trial. Discovery of potent and orally active lipoproteinassociated. This concept provides further support for the idea that atherosclerosis is a systemic.
Original article from the new england journal of medicine lipoproteinassociated phospholipase a2 as an independent predictor of coronary heart disease. The aim of this study is to evaluate the levels of serum lipoprotein. Association of lipoproteinassociated phospholipase a2 with the prevalence of nonalcoholic fatty liver disease. Lipoproteinassociated phospholipase a2 mass and activity and. Lipoprotein associated phospholipase a2 blood test.
Lipoproteinassociated phospholipase a2, vascular inflammation. The effect of darapladib on plasma lipoproteinassociated phospholipase a2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent. Albuminuria was present in 14% 22158 of participants at baseline, and 5% 486 of participants without albuminuria at baseline developed albuminuria until follow. The aim of this study was to analyze serum levels of lipoprotein phospholipase a 2 lppla 2 in patients with impaired bone resorption and correlate the findings with markers of bone metabolism osteocalcin and other biochemical markers. Two most notable families are secreted and cytosolic phospholipases a2. Association of serum lipoproteinassociated phospholipase. Pla2 mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively. Herein, we describe the discovery of a series of pyrimidone derivatives as lppla2 inhibitors. Elevated levels of serum lppla 2 are indicative of rupture prone plaque and a strong independent predictor of cardiovascular risk, including coronary artery. To analyze the performance characteristics, stability, and clinical value of lipoprotein associated phospholipase a2 lppla2 using an enzy we use cookies to enhance your experience on our website. Studies were included if they reported lppla2 mass andor activity levels and adjusted risk estimates of stroke. Lipoproteinassociated phospholipase a2 lppla2 is an inflammatory marker with certain vascular specificity and can be an independent risk factor for the pathological development of coronary heart disease.
Resveratrol is a naturally occurring polyphenolic compound with known cardioprotective, anti. Us7314742b2 lipoprotein associated phospholipase a2. Lipoproteinassociated phospholipase a2 activity is associated with risk of coronary heart disease and ischemic stroke. Lipoprotein associated phospholipase a2 and its association with cardiovascular outcomes in patients with acute coronary syndromes in the prove ittimi 22 pravastatin or atorvastatin evaluation and infection therapythrombolysis in myocardial infarction trial. Lysophosphatidylcholine increases the expression of vascular adhesion molecules, upregulates cytokines and cd40 ligand, and stimulates macrophage proliferation. Carotid artery color doppler ultrasonography and plasma. Lipoproteinassociated phospholipase a 2 lppla 2 also known as plateletactivating factor acetylhydrolase pafah is a phospholipase a 2 enzyme that in humans is encoded by the pla2g7 gene. It is predominantly produced by macrophages, lymphocytes and foam cells in atherosclerotic plaques and expressed in higher concentrations in advanced atherosclerotic lesions than earlystage lesions. Higher levels of lipoprotein associated phospholipase a2.
Pla2 in diabetes mellitus is controversial and analyses, especially in adolescents with type 2 diabetes t2d, are missing. Plasma lipoproteinassociated phospholipase a2 activity in. Lipoproteinassociated phospholipase a2 lppla2 is considered to be a promising therapeutic target for several inflammationassociated diseases. Lipoproteinassociated phospholipase a 2 is a phospholipase that complexes with ldl and catalyzes the release of proinflammatory lipid mediators.
However, the important limitation of the conventional enzymelinked immunosorbent assay plac elisa for lppla 2 assay is its relatively low sensitivity and time consuming. A specific and robust immunoassay for the lipoproteinassociated phospholipase a 2 lppla 2, plateletactivating factor acetylhydrolase, is described for the first time the immunoassay was used to evaluate possible links between plasma lppla 2 levels and atherosclerosis risk amongst susceptible individu. Human a2 phospholipases pla2s propagate inflammation by producing arachidonic acid precursors from membrane glycerophospholipids, which suggests this enzyme system as a promising drug target. Ldl and lpa undergo oxidation by reactive oxygen species ros in the aortic valve. Lipoproteinassociated phospholipase a 2 lppla 2 is an enzyme that has demonstrated proinflammatory properties. Lipoproteinassociated phospholipase a 2 lppla 2 is a proinflammatory enzyme secreted by macrophages. This test looks for a specific lipoprotein, lppla2, in your blood. Lipoproteinassociated phospholipase a2 as an independent. Lipoproteinassociated phospholipase a2 lppla2 is closely related to the development of atherosclerosis. Structureguided discovery of novel, potent, and orally.
Lppla2 hydrolyzes plateletactivating factor paf and oxidizes phospholipids with a modified short fatty acyl chain esterified at the sn2 position. The association between lipoproteinassociated phospholipase a2 lppla2 and stroke risk is inconsistent. Odonoghue m, morrow da, sabatine ms, murphy sa, mccabe ch, cannon cp, braunwald e. Lipoproteinassociated phospholipase a2, vascular inflammation and cardiovascular risk prediction. Lipoproteinassociated phospholipase a2, a marker of vascular.
Role of lipoproteinassociated phospholipase a2 in atherosclerosis. Lipoproteinassociated phospholipase a2 is associated with. Lipoproteinassociated phospholipase a 2 lppla 2 is a vascularspecific inflammatory enzyme belonging to the a2 phospholipase superfamily. To investigate this possibility, we analysed lowdensity lipoprotein ldl particle size and lipoproteinassociated phospholipase a2 lppla2 activity, both of which have been associated with increased cvr in the general population 1517. Of the five major pla2 classes,1 two have been implicated in the progression of atherosclerosis and its complications. Lipoproteinassociated phospholipase a2 and aortic stenosis.
Lipoproteinassociated phospholipase a2, highsensitivity. The lipoprotein associated phospholipase a2 lppla2plac test is typically used to assess a persons risk for certain types of cardiovascular disease as well as events like a heart attack. Lipoproteinassociated phospholipase a2 pathophysiological. We assessed lppla 2 and creactive protein crp levels along with traditional risk factors to examine their relation to ischemic stroke. The effect of darapladib on plasma lipoprotein associated phospholipase a2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent. In the last decades, the role of inflammation in the pathogenesis of atherosclerosis has been the topic of intense research. Lipoproteinassociated phospholipase a2 lppla2 is a promising therapeutic target for atherosclerosis, alzheimers disease, and diabetic macular edema. Current guidelines for assessing cardiovascular risk in hivinfected patients suggest that lppla 2 may be a useful surrogate marker for cvd health in.
Phospholipases a2 include several unrelated protein families with common enzymatic activity. Higher levels of lipoprotein associated phospholipase a2 is. Lipoproteinassociated phospholipase a2 lppla2 is an enzyme that is produced by. Lipoprotein associated phospholipase a2 lppla2 is an inflammatory marker with certain vascular specificity and can be an independent risk factor for the pathological development of coronary heart disease. An effort in this direction is presented by herrmann et al. Lipoproteinassociated phospholipase a2 as an independent predictor of coronary heart disease. The lppla2, which can hydrolyze oxidized phospholipids and then produce lysophosphatidylcholine and nonesterified fatty acids, causes endothelial dysfunction and takes part in the formation of.
Lipoproteinassociated phospholipase a 2 lppla 2 catalyzes the synthesis of proinflammatory lipids that recruit monocytes. Lipoproteinassociated phospholipase a2, plateletactivating. Lipoproteinassociated phospholipase a2 mass and activity. Here we report the identification of novel sulfonamide scaffold lppla2 inhibitors derived from a relatively weak fragment. Lipoproteinassociated phospholipase a2 lppla 2 is an enzyme that is expressed by inflammatory cells. Lipoprotein associated phospholipase a 2 lppla 2, an inflammatory enzyme expressed in atherosclerotic plaques, is a therapeutic target being assessed in trials of vascular disease prevention. Jan 01, 2015 lipoprotein associated phospholipase a2 lppla 2 is an enzyme that is expressed by inflammatory cells. Pdf lipoproteinassociated phospholipase a2 lppla2 also known as serum platelet activating factor acetylhydrolase pafah.
Research design and methods we conducted a nested, casecontrol study n 1,008 within a populationbased. The aim of this study was to assess the effects of darapladib, a selective oral investigational. Lipoprotein associated phospholipase a2 lppla 2 is a novel inflammatory biomarker, which is useful as an adjunct identification tool for cardiovascular disease. The aim of this study is to establish lipoprotein associated phospholipase a2 lppla2 reference intervals ris in healthy chinese han adults as a clinical diagnostic indicator according to the clinical and laboratory standards institute clsi c28a3 guidelines. Pla2 was identified as a strong predictor for cardiovascular events. Disposition of darapladib was compared following single i. Lipoprotein associated phospholipase a2 lppla2 as an. However, the association between the a379v polymorphism and formation of carotid plaques is unclear. Systematic structural modifications led to the identification of several pyrimidone compounds with promising in vitro inhibitory potency and. Add to favorites download citations track citations. Lipoproteinassociated phospholipase a2 lppla2 is a member of phospholipases superfamily which can hydrolyze oxidative phospholipid in low density lipoprotein ldl, and produce two. Lipoproteinassociated phospholipase a2 and risk of. Lipoproteinassociated phospholipase a 2 lppla 2is so named because it is found in human plasma largely associated with lowdensity lipoprotein ldl.
Performance characteristics and clinical value of the. The test is used to help predict your risk for cardiovascular disease and stroke. Lipoproteinassociated phospholipase lppla 2, originally called plateletactivating factor acetylhydrolase, is produced mainly by mature macrophages and lymphocytes and is influenced by a variety of inflammatory mediators. Lipoproteinassociated phospholipase a2 and coronary heart. Therefore, this study attempted to elucidate this issue. Hytest ltd intelligate 1, 6th fioor, joukahaisenkatu 6 fi20520 turku, finland tel. Lipoproteinassociated phospholipase a2 lppla2 is a novel and unique biomarker highly specific for vascular inflammation and atherosclerosis. Lipoprotein associated phospholipase a2, inhibitors thereof and use of the same in diagnosis and therapy download pdf info publication number us7217535b2. Pla 2 is associated with the risk of cardiovascular disease. Pdf lipoproteinassociated phospholipase a2 lppla2 activity.
Evaluation of lipoproteinassociated phospholipase a2 in. A total of 123 subjects with hyperlipidemia and 68 systemically healthy controls were included in the study. Although initial studies showed that lppla2 might be protective against atherosclerosis, emerging data seem to suggest that lppla2 may be proatherogenic, which is an effect thought to be mediated by lysophosphatidylcholine and oxidized nonesterified fatty. The aim of this study was to analyze serum levels of lipoprotein phospholipase a 2 lppla 2 in patients with impaired bone resorption and correlate the findings with markers of bone metabolism osteocalcin and other. Lppla2 mediates formation of bioactive mediators lysophosphatidyl choline and. Lipoproteinassociated phospholipase a 2 lppla 2, an inflammatory enzyme expressed in atherosclerotic plaques. Lipoproteinassociated phospholipase a2 and risk of coronary disease, stroke, and mortality. Association of lipoproteinassociated phospholipase a2 with. Lipoproteinassociated phospholipase a2 lppla2 is an emerging inflammatory marker that is used to assess the risk for cardiovascular disease cvd and associated events. This study was undertaken to assess the role of lipoprotein associated phospholipase a2 lp pla2 as a biomarker to predict cvd in patients with metabolic syndrome ms among south indian population. Lppla 2 has been explored as a target for a number of inflammation associated diseases, including cardiovascular disease and dementia.
Chemiluminescence immunoassay for sensing lipoprotein. We investigated associations of circulating lppla 2 mass and activity with risk of coronary heart disease, stroke, and mortality under different circumstances. Lipoproteinassociated phospholipase a2 distribution among. Lppla2 is an enzyme which is usually bound to ldl, often called the bad cholesterol, in the blood. We assessed lppla2 and creactive protein crp levels along. Lppla2 is an enzyme specific to arterial inflammation making it a promising biomarker for predicting the development of cvd. Mutations in lipoproteinassociated phospholipase a2 lppla2 are related to atherosclerosis. To date, evidence has emerged from epidemiologic studies of an increased risk of cvd events in individuals with elevated levels of circulating lipoproteinassociated phospholipase a 2 lppla 2. The immunoassay was used to evaluate possible links between plasma lppla 2 levels and atherosclerosis risk amongst susceptible individuals. Similarity searching on this fragment followed by molecular docking leads to the discovery of a micromolar inhibitor. Lppla2 levels in 763 healthy chinese han subjects 392 males and 371 females were determined by colorimetric analysis and the. Association of lipoproteinassociated phospholipase a2. Several markers of inflammation have shown predictive value for first.
Lipoprotein associated phospholipase a2 lppla2 is a proinflammatory enzyme secreted by macrophages. The a379v gene polymorphism, located in exon 11 of the pla2g7 gene, can affect lppla2 levels and the inflammatory response. It is secreted by macrophages and able to hydrolyse oxidised fatty acids from oxidised phospholipids in ldl thereby releasing proatherogenic lysophosphatidylcholine and fatty acids. Lipoproteinassociated phospholipase a2 is increased in. Previous reports have demonstrated that lipoprotein associated phospholipase a2 lppla2, an enzymatic inflammatory biomarker, is associated with increased risk of cardiovascular events 11. Lipoproteinassociated phospholipase a2 health encyclopedia. Lipoproteinassociated phospholipase a2 lppla2 is an enzyme that belongs to the superfamily of phospholipase a2 enzymes. New insights into the role of lipoproteinaassociated. Such an investigation was important because lppla 2 participates in the oxidative. Antioxidant and inflammatory aspects of lipoprotein. Lipoprotein associated phospholipase a2 lppla2 is a unique circulating phospholipase with inflammatory and oxidative activities and the limited data regarding the relationship between lppla2. Lipoproteinassociated phospholipase a2 is a specific vascular inflammatory marker, a risk factor, a prognostic biomarker. Lowdensity lipoprotein size and lipoproteinassociated.
Nov 28, 2005 background measurement of inflammatory markers has been reported to identify individuals at increased risk for ischemic stroke. Previous reports have demonstrated that lipoproteinassociated phospholipase a 2 lppla 2, an enzymatic inflammatory biomarker, is associated with increased risk of cardiovascular events. We cannot totally exclude the possibility of selection bias in that relative healthy individuals may be more likely to refuse to participate in the free. Lipoproteinassociated phospholipase a2 an overview.
Pdf lipoproteinassociated phospholipase a2 lppla 2. The utility of the lipoproteinassociated phospholipase a2. Lipoproteinassociated phospholipase a2 lppla2 is a monomeric enzyme that catalyzes oxidized. Disposition and metabolism of darapladib, a lipoprotein. Lppla 2 mediates formation of bioactive mediators lysophosphatidyl choline and oxidized nonesterified fatty acids known to elicit several deleterious inflammatory responses. The effect of darapladib on plasma lipoproteinassociated phospholipase a 2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent. Highsensitivity creactive protein, lipoproteinassociated. Lipoproteinassociated phospholipase a2, a marker of. Coronary heart disease, lipoprotein associated phospholipase a2, darapladib, inflammation, myocardial infarction, atherosclerosis. Lipoproteinassociated phospholipase a2, highsensitivity c.
Lipoproteinassociated phospholipase a2 activity and mass. Lipoproteinassociated phospholipase a2 lppla 2 is a novel inflammatory biomarker, which is useful as an adjunct identification tool for cardiovascular disease. Objective to investigate the association of lipoproteinassociated phospholipase a2 lppla2 mass and activity with incident cardiovascular disease cvd in a population with high prevalences of insulin resistance and diabetes, conditions for which epidemiological data remain sparse. It has been linked to cvd risk plaque formation and instability specifically in patients with underlying inflammatory disease. This particular phospholipase specifically recognizes the sn2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing arachidonic acid and lysophosphatidic acid. Lppla 2 is a calciumindependent phospholipase a2 enzyme that is associated with both lowdensity lipoprotein ldl and, to a lesser extent, highdensity lipoprotein hdl in human plasma and serum 1 and is distinct from other such phospholipases such as cpla 2 and spla 2. Both proatherogenic property of lppla2 and positive correlation with cv events have already been demonstrated by a large number of. Sep 28, 2011 odonoghue m, morrow da, sabatine ms, murphy sa, mccabe ch, cannon cp, braunwald e. Lipoproteinassociated phospholipase a2 lppla 2isa novel biomarker of vascularspecific inflammation that provides information about atherosclerotic plaque inflammation and stability. Lipoproteinassociated phospholipase a2 lppla2 is a unique circulating phospholipase with inflammatory and oxidative activities and the limited data regarding the. The role of lipoproteinassociated phospholipase a2 as a.
Change in lipoproteinassociated phospholipase a2 and its. We investigated associations of circulating lppla 2 mass and activity with risk of coronary heart disease, stroke, and mortality under different. Lipoprotein associated phospholipase a2 lppla2 is a member of phospholipases superfamily which can hydrolyze oxidative phospholipid in low density lipoprotein ldl, and produce two. Lipoproteinassociated phospholipase a 2 lppla2, a leukocytederived enzyme involved in the metabolism of lowdensity lipoprotein ldl cholesterol to proinflammatory mediators, 9 has also been shown in prospective studies 10,11 to predict incident stroke independent of hscrp. Lipoprotein associated phospholipase a2 lppla2 is considered to be a promising therapeutic target for several inflammation associated diseases. Lipoprotein associated phospholipase a2 does this test have other names. A specific and robust immunoassay for the lipoprotein associated phospholipase a 2 lppla 2, plateletactivating factor acetylhydrolase, is described for the first time. Background measurement of inflammatory markers has been reported to identify individuals at increased risk for ischemic stroke. The absorption, metabolism, and excretion of darapladib, a novel inhibitor of lipoproteinassociated phospholipase a2, was investigated in healthy male subjects using 14cradiolabeled material in a bespoke study design. Effect of treatment for 12 weeks with rilapladib, a. Antioxidant and inflammatory aspects of lipoproteinassociated. Us7217535b2 lipoprotein associated phospholipase a2.
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