Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, atherosclerosis has become recognized as an inflammatory disease whose activity can be assessed by circulating biomarkers. Along with C-reactive protein (CRP), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) may now be considered as a biomarker with sufficient accumulated evidence to support its application in clinical practice. Lp-PLA(2) is especially appealing because of its vascular specificity, which directly derives from its role in plaque pathophysiology. This article reviews the highlights of the >25 prospective epidemiologic studies now published on Lp-PLA(2) as a risk marker in primary or secondary prevention. These trials demonstrate generally consistent correlations between elevated Lp-PLA(2) levels and the increased risk for cardiovascular events, even after multivariable adjustment for traditional risk factors, with roughly a doubling of risk associated with upper quantile levels. Furthermore, Lp-PLA(2) as a risk predictor has been shown to be independent of and complementary to high-sensitivity CRP. These study results combined with recommendations from the American Heart Association/Centers for Disease Control (AHA/CDC) and the National Cholesterol Education Program III (NCEP III) suggest that Lp-PLA(2) might best be used in current clinical practice to refine risk prediction in those at intermediate cardiovascular risk. An increasingly prevalent group at intermediate risk shown to benefit from Lp-PLA(2) risk modification is the population with the cardiovascular metabolic syndrome, clinically identified as overweight patients with features of mixed dyslipidemia, dysglycemia, and hypertension. An additional application supported by these studies is further risk stratification of high- (often secondary-) risk patients into a group at very high risk, for whom a more aggressive target for low-density lipoprotein of <70 mg/dL (1 mg/dL = 0.02586 mmol/L) is now recommended as a reasonable therapeutic goal.
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PMID:Lipoprotein-associated phospholipase A2: an independent predictor of coronary artery disease events in primary and secondary prevention. 1854 68

Stroke is the second-leading cause of death worldwide and is a disabling disease of both older and younger adults. Stroke is also among the most highly preventable disorders because there are well-defined risk factors and preventatives. The establishment of new risk markers or factors for stroke risk assessment provides a new avenue for stroke prevention. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an enzyme that hydrolyzes oxidized phospholipids, releasing lysophosphatidylcholine, which has proinflammatory properties thought to be involved in the development of atherosclerosis and plaque rupture. In 2005, the Lp-PLA(2) blood test was approved by the US Food and Drug Administration (FDA) for assessing the risk of ischemic stroke and coronary artery disease. In epidemiologic studies, low-density lipoprotein cholesterol and other lipid factors have not been shown to be consistent predictors of stroke risk. Lp-PLA(2) measures, on the other hand, have shown a consistent association with stroke risk, conferring about a 2-fold increase in stroke occurrence. This relation has been studied in both first and recurrent stroke and is reviewed in this article. Importantly, a recent study has now shown that Lp-PLA(2) may increase the area under the curve beyond that of traditional cardiovascular risk factors and C-reactive protein. Therefore, Lp-PLA(2) determination may provide a pivotal opportunity to appropriately classify previously misclassified persons who are actually at high risk of stroke and in need of aggressive stroke intervention.
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PMID:Lipoprotein-associated phospholipase A2 and risk of stroke. 1854 70

A substantial body of peer-reviewed studies has been published validating the role of inflammation in atherogenesis and supporting lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) as a cardiovascular risk marker independent of and additive to traditional risk factors. As with elevated high-sensitivity C-reactive protein, an elevated Lp-PLA(2) level approximately doubles the risk for primary and secondary cardiovascular events. Interestingly, when both inflammatory markers are increased together, they provide an even greater predictive capability to help identify very-high-risk individuals who would benefit most from aggressive lipid-lowering therapy. High levels of Lp-PLA(2) are present in inflamed, rupture-prone plaques, and it appears that Lp-PLA(2) is released from these plaques into the circulation. Over 25 prospective epidemiologic studies have demonstrated the association of elevated Lp-PLA(2) levels with future coronary events and stroke-11 of 12 prospective studies have shown a statistically significant association between elevated Lp-PLA(2) and primary coronary or cardiovascular events, 12 of 13 have shown a statistically significant association with recurrent coronary or cardiovascular events, and 6 studies have shown a positive association with stroke. Lp-PLA(2) should be viewed today as an important cardiovascular risk marker whose utility is as an adjunct to the major risk factors to adjust absolute risk status and thereby modify low-density lipoprotein cholesterol goals. The low biologic fluctuation and high vascular specificity of Lp-PLA(2) makes it possible to use a single measurement in clinical decision making, and it also permits clinicians to follow the Lp-PLA(2) marker serially. Ultimately, Lp-PLA(2) may also be classified as a risk factor, but this should not detract from its utility today as a risk marker.
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PMID:Review of the evidence for the clinical utility of lipoprotein-associated phospholipase A2 as a cardiovascular risk marker. 1854 71

The cardio protective effect of estrogen in women has come under scrutiny as recent evidence from long-term trials has demonstrated negative findings. In contrast, the effect of endogenous sex hormones, specifically estrogen, on cardiovascular disease, inflammation and clotting parameters in men has not been well-studied. Men receiving androgen deprivation therapy for prostate cancer provide a unique model to study the effect of estrogen alone on inflammation and clotting factors. In a short-term randomized controlled trial of 17-beta estradiol (E(2)) versus placebo, we measured sex hormones, markers of inflammation including homocysteine (HC), C-reactive protein (CRP), interleukin-6 (IL-6) and coagulation factors including fibrinogen, plasminogen activator-inhibitor-1 (PAI-1) and anti-thrombin-III (AT-III) in 27 older men without bone metastases receiving androgen deprivation therapy or neoadjuvant treatment for prostate cancer. After 9 weeks of E(2) treatment, there was no difference in inflammation or clotting parameters between groups, but after 9 weeks of treatment AT-III increased in the E(2) treated group and decreased in the placebo group. CRP, homocysteine and IL-6 did not show any significant differences. We also evaluated the above parameters in 12 men 3 weeks after acute steroid withdrawal with androgen deprivation therapy and found no significant changes. We found an increase in AT-III in men receiving E(2) which may be related to gonadal steroid withdrawal, but no significant differences in other inflammatory or clotting factor parameters. While the current report is very preliminary in a small group of subjects, further studies are needed to determine the long-term effects of E(2) in this population of hypogonadal men.
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PMID:The effect of short-term estradiol therapy on clotting and inflammatory markers in older men receiving hormonal suppression therapy for prostate cancer. 1857 58

Increased inflammation, fibrinolytic factors, and lipoprotein(a) (LP[a]) were associated with increased cardiovascular events in patients with type 2 diabetes, whereas higher levels of cardiorespiratory fitness (CRF) were associated with a lower incidence of cardiovascular mortality. Whether CRF is associated with inflammatory markers, fibrinolytic factors, and LP(a) in patients with type 2 diabetes was investigated. A total of 425 men with type 2 diabetes (mean age 55 +/- 8 years) who participated in a medical screening program were studied. CRF was measured using peak oxygen uptake with expired gas analysis during a symptom-limited exercise test. CRF inversely correlated with C-reactive protein (CRP; r = -0.27, p <0.05), white blood cell count (r = -0.13, p <0.05), fibrinogen (r = -0.28, p <0.05), LP(a) (r = -0.53, p <0.05), tissue plasminogen activator (t-PA) antigen (r = -0.65, p <0.05), and plasminogen activator inhibitor-1 activity (r = -0.17, p <0.05). Men in the highest tertile of CRF had significantly lower CRP, white blood cell count, fibrinogen, LP(a), and t-PA than men in the lowest tertile of CRF (all p <0.05). In separate multivariable linear regression models that adjusted for age, body mass index, smoking, lipid profiles, glucose, and systolic blood pressure, CRP (beta = -0.23, p <0.05), white blood cell count (beta = -0.16, p <0.05), fibrinogen (beta = -0.24, p <0.05), LP(a) (beta = -0.28, p <0.05), and t-PA (beta = -0.69, p <0.05) were each inversely associated with CRF. Each MET increment higher peak oxygen uptake was associated with a lower odds ratio of having abnormal LP(a) (odds ratio 0.43, 95% confidence interval 0.20 to 0.91) in a multivariate logistic regression model. In conclusion, CRF was inversely associated with inflammatory markers, fibrinolytic factors, and LP(a) in men with type 2 diabetes.
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PMID:Relation of cardiorespiratory fitness to inflammatory markers, fibrinolytic factors, and lipoprotein(a) in patients with type 2 diabetes mellitus. 1877 91

We investigated the effect of atorvastatin monotherapy and combined treatment with atorvastatin and pioglitazone on intima-media thickness, vascular function and the cardiovascular risk profile. In all, 148 patients (76 male, 72 female; aged 61.4+/-6.5 years; body mass index [BMI] 29.2+/-4.1 kg/m2; mean +/- SD) with increased cardiovascular (CV) risk factors were randomised. Intima-media thickness (IMT), the augmentation index (Aix@75), the microvascular response to acetylcholine (LDF), lipid status, and plasma levels of intact proinsulin, adiponectin, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), sCD40L, P-selectin, tissue plasminogen activator (t-PA) and blood lipids were monitored over six months. Atorvastatin treatment, alone and in combination with pioglitazone, revealed a significant regression in IMT (0.923+/-0.013 to 0.874+/-0.012 mm and 0.921+/-0.015 to 0.882+/-0.015 mm; mean +/- SEM; p<0.05 respectively) and Aix@75 (27.3+/-1.2 to 25.9+/-1.4; and 25.6+/-1.4 to 24.8+/-1.7%; p<0.05). The endothelial response to acetylcholine as measured by laser Doppler fluximetry (LDF) improved during combined treatment (373+/-57 to 576+/-153 AU; p<0.05). Addition of pioglitazone to atorva-statin resulted in significant further effects on high-sensitivity C-reactive protein (hsCRP), t-PA, P-selectin, adiponectin, triglycerides and high-density lipoprotein (HDL) cholesterol (p<0.05 respectively). Atorvastatin significantly improved IMT and vascular elasticity. Co-administration of pioglitazone provided additional effects on endothelial function, lipid profile and laboratory markers of inflammation.
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PMID:Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk. 1895 40

The inflammatory marker, C-reactive protein (CRP) is associated with long-term cardiovascular events. The aim of the study was to investigate the factors contributing to serum CRP, assess the relationship between CRP level and the parameters of visceral obesity, and examine the association between leptin and CRP level in type 2 diabetic patients. 150 patients with type 2 diabetes were enrolled. These patients were recently diagnosed (< or =3 years) with type 2 diabetes and were drug naive or taking sulfonylureas only. BMI, WC, and serum concentration of CRP, glycosylated hemoglobin (HbA1c), glucose, lipids, plasminogen activator-1 (PAI-1) and leptin were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). We measured the carotid intima-media thickness (IMT). Fat mass assessed by dual-energy X-ray absorptionmetry and abdominal fat distribution was determined by CT scan. Serum concentration of CRP was significantly correlated with BMI (gamma = 0.257, P < 0.01), WC (gamma = 0.293, P < 0.01), fat mass (gamma = 0.213, P < 0.01), total adipose tissue (gamma = 0.263, P < 0.01), visceral adipose tissue (gamma = 0.296, P < 0.01), insulin (gamma = 0.189, P = 0.047), PAI-1 (gamma = 0.206, P < 0.01), leptin (gamma = 0.322, P < 0.01), mean IMT (gamma = 0.132, P = 0.042), and HOMA-IR (gamma = 0.172, P = 0.045). After adjustment for age and gender, multiple regression analysis showed that serum CRP was significantly associated with leptin (beta = 0.326, P = 0.01) and visceral adipose tissue (beta = 0.265, P = 0.035). In conclusion, serum CRP level is significantly associated with obesity, especially the visceral adipose tissue, and serum leptin is another important independent factor associated with CRP in Korean type 2 diabetic patients.
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PMID:Visceral adiposity and leptin are independently associated with C-reactive protein in Korean type 2 diabetic patients. 1941 64

Oxidative damage has been implicated in the pathogenesis of Parkinson disease (PD) but the literature data are confusing. Using products of lipid and DNA oxidation measured by accurate methods, we assessed the extent of oxidative damage in PD patients. The levels of plasma F(2)-isoprostanes (F(2)-IsoPs), hydroxyeicosatetraenoic acid products (HETEs), cholesterol oxidation products, neuroprostanes (F(4)-NPs), phospholipase A(2) (PLA(2)) and platelet activating factor-acetylhydrolase (PAF-AH) activities, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serum high-sensitivity C-reactive protein were compared in 61 PD patients and 61 age-matched controls. The levels of plasma F(2)-IsoPs, HETEs, 7beta-and 27-hydroxycholesterol, 7-ketocholesterol, F(4)-NPs, and urinary 8-OHdG were elevated, whereas the levels of plasma PLA(2) and PAF-AH activities were lower, in PD patients compared to controls (p< 0.05). The levels of plasma F(2)-IsoPs, HETEs, and urinary 8-OHdG were higher in the early stages of PD (p trend< 0.05). There was a significant negative correlation between the cumulative intake of levodopa and urinary 8-OHdG (r= -0.305, p= 0.023) and plasma total HETEs (r= -0.285, p= 0.043). Oxidative damage markers are systemically elevated in PD, which may give clues about the relation of oxidative damage to the onset and progression of PD.
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PMID:Oxidative damage in Parkinson disease: Measurement using accurate biomarkers. 1996 70

Given the paucity of data in type 1 diabetes concerning lipoprotein-associated phospholipase A( 2) (Lp-PLA(2)), we examined its prospective relationship with coronary artery disease (CAD), as well as the effect of modification by C-reactive protein (CRP) and haptoglobin genotype, in individuals with type 1 diabetes who are at an increased risk for CAD due to also having macroalbuminuria (n=96). Although Lp-PLA(2) activity was univariately predictive of CAD (HR=1.54 per SD, p=0.009), this relationship was not significant after covariate adjustment (p=0.59). There was a significant interaction between Lp-PLA(2) and CRP (p=0.02), i.e. those with both markers greater than the median level were more likely to have a CAD event than those persons with low levels of both (HR=2.89, p=0.06). When stratified by haptoglobin genotype, Lp-PLA(2) was predictive of CAD in persons with the 2/1 (HR=2.40, p=0.05), but not 2/2 (HR=0.66, p=0.27), genotype. The association between Lp-PLA(2) activity and CAD differs by CRP and haptoglobin genotype in this group of persons with type 1 diabetes and macroalbuminuria.
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PMID:Lipoprotein-associated phospholipase A2, C-reactive protein, and coronary artery disease in individuals with type 1 diabetes and macroalbuminuria. 2036 32

Hypofibrinolysis as measured with overall clot lysis assays is associated with risk of arterial thrombosis. Individual components of the fibrinolytic system, however, have not been studied extensively in relation to arterial disease, or results of studies were inconsistent. The relation between plasminogen and alpha2-antiplasmin levels and cardiovascular risk factors and the association between plasminogen, alpha2-antiplasmin, tissue-plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) and risk of myocardial infarction was investigated in the Study of Myocardial Infarctions Leiden (555 men with a first myocardial infarction and 635 controls). alpha2-antiplasmin was associated with age and lipid levels, whereas plasminogen correlated with lipids, C-reactive protein, and smoking. Increased levels of all fibrinolytic factors were associated with myocardial infarction. Age-adjusted odds ratios (ORs; 95% confidence interval) for quartile 4 compared with 1 were 1.7 (1.2-2.3) for plasminogen, 1.9 (1.3-2.6) for alpha2-antiplasmin, 1.7 (1.2-2.3) for t-PA, and 1.7 (1.2-2.4) for PAI-1. After adjusting for cardiovascular risk factors, only alpha2-antiplasmin levels remained associated with risk (OR, 1.4; [1.0-2.0]). t-PA and PAI-1 levels predominantly reflected lipid levels, whereas plasminogen reflected the inflammatory state. Concluding, elevated alpha2-antiplasmin levels are independently associated with risk of myocardial infarction. t-PA, PAI-1, and plasminogen levels appear to reflect other cardiovascular risk factors.
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PMID:Plasma levels of fibrinolytic proteins and the risk of myocardial infarction in men. 2041 57


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