Measurement of lipoproteinassociated phospholipase a2 in the. Methods studies were included if they reported lppla2 mass andor activity levels and adjusted risk estimates of stroke. Levels of hscrp, an acutephase reactant, increase with stroke severity and may be associated with mortality to a. Structural and thermodynamic characterization of protein. Accumulating evidence has suggested that lppla2 is a biomarker of cad and may have a proinflammatory role in the progression of atherosclerosis. Lipoprotein associated phospholipase a2 lp pla2 monoclonal antibody lot number. Measurement of lipoprotein associated phospholipase a2 lppla2 does not meet payment determination criteria as randomized controlled studies have not been conducted and other scientific evidence has not shown improved longterm health outcomes. 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. Measurement of lipoproteinassociated phospholipase a2 in. Measurement of lipoproteinassociated phospholipase a2. A total of 123 subjects with hyperlipidemia and 68 systemically healthy controls were included in. Association of lipoprotein associated phospholipase lppla 2 and highsensitivity creactive protein hscrp with incident ischemic stroke. Is lipoproteinassociated phospholipase a2 activity correlated with.
Lipoproteinassociated phospholipase a2 health encyclopedia. Albuminuria was present in 14% 22158 of participants at baseline, and 5% 486 of participants without albuminuria at baseline developed albuminuria until follow. We conducted a metaanalysis to determine whether elevated lppla2 is a risk factor for stroke. Multiple fragment hits were observed in different regions of the active site, including some hits that bound in a pocket created by movement of a protein side chain. Elevated levels of human lipoproteinassociated phospholipase a2 lppla 2 are associated with cardiovascular disease and dementia. Lipoproteinassociated phospholipase a2 as a predictive. Pdf lipoproteinassociated phospholipase a2 lppla2 activity. This test measures the amount or activity of lp pla 2 in the blood some recent studies have shown that lp pla 2 is an independent risk marker for cardiovascular disease cvd, including coronary. These findings necessitate the need for more reliable and accurate biomarkers to predict cvd. Coronary heart disease, lipoprotein associated phospholipase a2, darapladib, inflammation, myocardial infarction, atherosclerosis. Lipoproteinassociated phospholipase a2 activity is. Lipoproteinassociated phospholipase a2 as a predictive biomarker. Regulation of lipoproteinassociated phospholipase a2 silencing on myocardial fibrosis in mice with coronary atherosclerosis author links open overlay panel guozhong pan a lanjun kou a yang wu b yuanji hu a xiaoshuo lin a jinrui guo a xiaoxia ren a yan zhang a. Lipoproteinassociated phospholipase a2 lppla2, also known as platelet activating factor acetylhydrolase pafah, is a unique member of.
Lipoproteinassociated phospholipase a2 is a proinflammatory enzyme secreted by macrophages that is primarily bound to ldl in the circulation. Pla2 in diabetes mellitus is controversial and analyses, especially in adolescents with type 2 diabetes t2d, are missing. May 01, 2008 variability of lipoprotein associated phospholipase a2 measurements joseph p mcconnell address correspondence to this author at. Clinical chemistry, immunology and laboratory quality control, 2014.
Lipoprotein associated phospholipase a2 lppla2 is an emerging inflammatory marker that is used to assess the risk for cardiovascular disease cvd and associated events. Background lipoproteinassociated phospholipase a2 lppla2 has been proposed as an inflammatory marker of cardiovascular disease. Conclusions inflammatory markers are associated with prognosis after first ischemic stroke and may offer complementary information. Lipoproteinassociated phospholipase a2 lppla2 probably plays an important role in the development of acute coronary syndrome acs.
Lipoproteinassociated phospholipase a 2 lp pla 2 is an enzyme that appears to play a role in the inflammation of blood vessels and is thought to help promote atherosclerosis. In this context, lipoproteinassociated phospholipase a2 lppla2. Association of lipoproteinassociated phospholipase lppla 2 and highsensitivity creactive protein hscrp with incident ischemic stroke. Several epidemiologic studies have demonstrated an independent association between plasma lppla2 concentration and risk for cardiovascular events. Lipoproteinassociated phospholipase a2 and coronary heart. Exploitation of a novel binding pocket in human lipoprotein. 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.
High rigidity of lppla2 structure and similar binding modes of inhibitors with completely different. Lppla2 is an enzyme which is usually bound to ldl, often called the bad cholesterol, in the blood and plays a role in the inflammation of blood vessels. Lipoproteinassociated phospholipase a2 activity, ferritin levels, metabolic syndrome, and 10year cardiovascular and noncardiovascular mortality. Lipoproteinassociated phospholipase a2 and risk of coronary. Lipoproteinassociated phospholipase a2 lppla2 is an emerging inflammatory marker that is used to assess the risk for cardiovascular disease cvd and associated events. Pdf lipoproteinassociated phospholipase a2 lppla 2. Lipoproteinassociated phospholipase a2 lppla2 antigen profile protein summary the protein encoded by this gene is a secreted enzyme that catalyzes the degradation of plateletactivating factor to biologically inactive products. Elevated plasma lipoproteinassociated phospholipase a2 activity is associated with plaque rupture in patients with coronary artery disease.
However, alterations of lppla2 levels during acs and its association with cardiovascular outcome are unclear. Lipoproteinassociated phospholipase a2 lppla 2 is a novel biomarker of vascularspecific inflammation that provides information about atherosclerotic plaque inflammation and stability. Methods and results the rotterdam study is a populationbased followup study in 7983 subjects. Lipoproteinassociated phospholipase a2, vascular inflammation and cardiovascular risk prediction. Lipoproteinassociated phospholipase a2 lppla2 represents a promising therapeutic target for atherosclerosis and alzheimers disease. Our aim was to investigate the change in lppla2 and its association with cardiovascular outcome in patients with acs. Measurement of lipoproteinassociated phospholipase a2 lp. Methods a populationbased study of stroke risk factors in 467 patients with first ischemic stroke was undertaken to determine whether levels of highsensitivity creactive protein hscrp and lipoproteinassociated phospholipase a 2 lppla2 predict risk of stroke recurrence, other vascular events, and death. Pla2 mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its.
It is primarily produced by macrophages and other in. Lipoproteinassociated phospholipase a2 lppla2 immunoassay for prediction of risk for coronary heart disease or ischemic stroke plac test is investigative and therefore not covered. Lppla 2 activity is to be used in conjunction with clinical evaluation and patient risk assessment as an aid in predicting risk of coronary heart disease chd in patients with no prior history of cardiovascular events. Coronary heart disease, lipoproteinassociated phospholipase a2, darapladib, inflammation, myocardial infarction, atherosclerosis. Lipoproteinassociated phospholipase a2 lp pla2, also known as plateletactivating factor acetylhydrolase, is an enzyme that hydrolyzes phospholipids and is primarily associated with ldls. Measurement of lipoproteinassociated phospholipase a2 lppla2 in the assessment of cardiovascular risk 2 background lowdensity lipoproteins ldl have been identified as the major atherogenic lipoproteins and have long been identified by the national cholesterol education project ncep as the primary target of cholesterollowering therapy. The enzyme was identified by a second monoclonal antibody labeled with biotin and a streptavidinalkaline phosphatase conjugate.
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. Pafah catalyzes the removal of the acyl group at the sn2 position of paf and truncated. Lipoproteinassociated phospholipase a 2 lppla 2 is a specific biomarker specific for vascular inflammation. Lipoproteinassociated phospholipase a2 does this test have other names. Pla2 was identified as a strong predictor for cardiovascular events. Lipoproteinassociated phospholipase a2, highsensitivity creactive protein, and risk for incident coronary heart disease in middleaged men and women in the atherosclerosis risk in communities aric study. Accumulating evidence has suggested that lppla2 is a biomarker of coronary artery disease cad and. Odonoghue m, morrow da, sabatine ms, murphy sa, mccabe ch, cannon cp, braunwald e. Variability of lipoproteinassociated phospholipase a2. Lipoproteinassociated phospholipase a2 as an independent.
Role of lipoproteinassociated phospholipase a2 in vascular disease. Lipoproteinassociated phospholipase a 2 mass was measured with an enzymelinked immunoassay according to previously described methods. Lipoproteinassociated phospholipase a2 lppla2 pla2g7. Pdf lipoproteinassociated phospholipase a2 lppla2 also known as serum platelet activating factor acetylhydrolase pafah activity constitutes a. 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. Phospholipases a2 include several unrelated protein families with common enzymatic activity. Measurement of lipoprotein associated phospholipase a2. Describes how the lipoprotein associated phospholipase a2 lppla2 test is used, such as to help determine risk of developing cardiovascular disease, when the lppla2 test is ordered, and what the results of an lppla2 test might mean. Pdf lipoproteinassociated phospholipase a2 activity and. Lipoprotein associated phospholipase a2 and risk of coronary disease, stroke, and mortality. Measurement of lipoproteinassociated phospholipase page 2 of 14 a2 in the assessment of cardiovascular risk. Lipoproteinassociated phospholipase a2, vascular inflammation.
Lipoproteinassociated phospholipase a2, highsensitivity c. Lipoproteinassociated phospholipase a2 lppla2, also known as plateletactivating factor acetylhydrolase, is an enzyme that hydrolyzes phospholipids and is primarily associated with lowdensity lipoproteins ldls. In the last decades, the role of inflammation in the pathogenesis of atherosclerosis has been the topic of intense research. Ischemic stroke risk in individuals with elevated levels of both lppla 2 highest tertile and hscrp highrisk category as defined in the centers for disease control and preventionamerican heart association. Lipoprotein associated phospholipase a2 activity, ferritin levels, metabolic syndrome, and 10year cardiovascular and noncardiovascular mortality. Lipoproteinassociated phospholipase a2 has been shown to be an independent risk factor for coronary heart disease and ischemic stroke in several studies. Several markers of inflammation have shown predictive value for first.
This test looks for a specific lipoprotein, lppla2, in your blood. Ischemic stroke risk in individuals with elevated levels of both lppla 2 highest tertile and hscrp highrisk category as defined in the centers for disease control and preventionamerican heart association guidelines 19 was more than 11 times. See also related mtac coverage policy, lipoprotein subclass testing for screening, evaluation, and monitoring of cardiovascular disease. Lipoprotein associated phospholipase a2 lppla 2 is a novel biomarker of vascularspecific inflammation that provides information about atherosclerotic plaque inflammation and stability. Lipoprotein associated phospholipase a2 the journal of lipid. The plac test for lppla 2 activity is an enzyme assay for the in vitro quantitative determination of lppla 2 lipoproteinassociated phospholipase a2 activity in edta plasma and serum. Background lipoproteinassociated phospholipase a2 lppla2 is expressed abundantly in the necrotic core of coronary lesions, and products of its enzymatic activity may contribute to.
Here we reported the first crystal structures of lppla2 bound with reversible inhibitors and the thermodynamic characterization of complexes. Role of lipoproteinassociated phospholipase a2 in atherosclerosis. Lipoprotein associated phospholipase a2 lppla2, has inflammatory and atherogenic effect on vasculature. Lipoproteinassociated phospholipase a2 lppla2 antibodies. Lipoproteinassociated phospholipase a2 lppla2 protein profile protein summary the protein encoded by this gene is a secreted enzyme that catalyzes the degradation of plateletactivating factor to biologically inactive products. Lipoproteinassociated phospholipase a2 lp pla2 clinical and research area cardiac markers clinical utility prognostic marker of adverse cardiacrelated events 1. Effects of the direct lipoproteinassociated phospholipase. Evidence has gathered that inflammation plays a crucial. The standard was purified lipoproteinassociated phospholipase a. Performance characteristics and clinical value of the. Elevated plasma lipoprotein associated phospholipase a2 activity is associated with plaque rupture in patients with coronary artery disease. Lipoproteinassociated phospholipase a2 lppla2 is a calciumindependent phospholipase a2 enzyme secreted by leukocytes and associated with circulating lowdensity lipoprotein and macrophages in atherosclerotic plaques. Is lipoproteinassociated phospholipase a2 activity correlat.
Lipoproteinassociated phospholipase a2 request pdf. Highsensitivity creactive protein, lipoproteinassociated. Lipoprotein associated phospholipase a2 lppla2 is a monomeric enzyme that catalyzes oxidized phospholipid found in ldl into lysophosphatidylcholine and oxidized fatty acid, both of which are atherogenic. Lipoproteinassociated phospholipase a 2 may be a stronger predictor of recurrent stroke risk. Request pdf lipoproteinassociated phospholipase a2 cardiovascular disease cvd is the number one cause of death in both adult men and women. Change in lipoproteinassociated phospholipase a2 and its as.
Informations about lipoprotein associated phospholipase a2 lppla2 pla2g7 antibody hrp abx108616100. Two most notable families are secreted and cytosolic phospholipases a2. Lipoproteinassociated phospholipase a2 an overview. Lipoproteinassociated phospholipase a2 and its relationship with markers of subclinical cardiovascular disease. Effects of the direct lipoproteinassociated phospholipase a2. The test is used to help predict your risk for cardiovascular disease and stroke. 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. Pla2 mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation.
Elevated levels of human lipoprotein associated phospholipase a2 lppla 2 are associated with cardiovascular disease and dementia. Pdf recent developments with lipoproteinassociated. Lipoprotein associated phospholipase a2 lppla2 is a calciumindependent phospholipase a2 enzyme secreted by leukocytes and associated with circulating lowdensity lipoprotein and macrophages in atherosclerotic plaques. Lipoproteinassociated phospholipase a2, highsensitivity. Lipoprotein associated phospholipase a2 lppla2 antigen profile protein summary the protein encoded by this gene is a secreted enzyme that catalyzes the degradation of plateletactivating factor to biologically inactive products. 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. Antioxidant and inflammatory aspects of lipoprotein. Growing evidence suggests that the mass and activity of lppla 2 are positively correlated with an increased risk of developing coronary artery disease and stroke 1. Pla2 mediates vascular inflammation through the regulation of lipid metabolism in blood, thus.
Lipoproteinassociated phospholipase a2 lppla2 is an enzyme that is produced by inflammatory cells, cotravels with circulating lowdensity. We read with interest the recent report in this journal by khuseyinova and colleagues regarding the variability of serial lipoproteinassociated phospholipase a2 lppla2 measurements in postmyocardial infarction patients. Is lipoprotein associated phospholipase a2 activity correlated with. Pla2 belongs to group vii of the pla2 superfamily, which currently comprises of six types and is divided into 16 unique groups. Background the association between lipoproteinassociated phospholipase a2 lppla2 and stroke risk is inconsistent. Department of laboratory medicine and pathology mayo clinic hilton 310a 200 first st sw rochester, mn 55905 fax 507 2662888 email mcconnell. Lppla 2 also termed plateletactivating factor acetylhydrolase is a 45. A fragment screen was conducted against lppla 2 in order to identify novel inhibitors. Multiple fragment hits were observed in different regions of the active site, including some hits that bound in a pocket. Regulation of lipoprotein associated phospholipase a2 silencing on myocardial fibrosis in mice with coronary atherosclerosis author links open overlay panel guozhong pan a lanjun kou a yang wu b yuanji hu a xiaoshuo lin a jinrui guo a xiaoxia ren a yan zhang a. Lipoprotein associated phospholipase a2 lppla2 as an. Antioxidant and inflammatory aspects of lipoproteinassociated.
This chapter is focused on the plasma form of pafacetylhydrolase pafah, a lipoproteinbound, calciumindependent phospholipase a 2 activity also referred to as lipoproteinassociated phospholipase a2 and pla2g7. Because lppla2 plays a role in inflammation but, unlike other inflammatory proteins, is not an acutephase reactant. Ballantyne and colleagues 7 studied lppla2 in the 12,762 apparently healthy individuals participating in the aric study. Lipoproteinassociated phospholipase a2 lppla2 is an enzyme that exhibits proinflammatory properties and has been associated with subclinical cardiovascular disease. The lipoproteinassociated 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. Hence, we examine the impact of high lppla2 levels on endothelial function and arterial stiffness of patients with coronary artery disease cad. Background lipoproteinassociated phospholipase a2 lppla2 is expressed abundantly in the necrotic core of coronary lesions, and products of its enzymatic activity may contribute to inflammation. Change in lipoproteinassociated phospholipase a2 and its. Lipoprotein associated phospholipase a2 as an independent. A total of 123 subjects with hyperlipidemia and 68 systemically healthy controls were included in the study. Is lipoproteinassociated phospholipase a2 activity. Lipoproteinassociated phospholipase a2 lppla2, also known as plateletactivating factor acetylhydrolase, is an enzyme that. 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. The aim of this study is to evaluate the levels of serum lipoprotein.
In the present study, we investigated whether lppla2 is an independent predictor of coronary heart disease and ischemic stroke. Pdf lipoproteinassociated phospholipase a2 activity. Lipoproteinassociated phospholipase a2 test request a test. Lipoproteinassociated phospholipase a2 and risk of. 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. Regulation of lipoproteinassociated phospholipase a2. Elevated levels of serum lppla 2 are indicative of rupture prone plaque and a strong independent predictor of cardiovascular risk, including coronary artery.
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