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)

Stress hormones, tissue-plasminogen activator (t-PA) antigen, left-ventricular diastolic function and mood immediately before and after listening to three different kinds of music (a waltz by J. Strauss, a piece of modern classic by H. W. Henze, and meditative music by R. Shankar) were measured in 20 healthy persons (10 women, 10 men; mean age 25 [20-33] years) and 20 hypertensives (8 women, 12 men; mean age 57.5 [25-72] years). To recognise haemodynamic effects, mitral flow by Doppler ultrasound was used as a measure of left-ventricular diastolic function. Atrial filling pressure (AFF) was calculated from the flow integral (VTI) of the early E and the late A waves. The Zerssen scale was used to estimate the immediate mood of the subjects. In hypertensives the levels of cortisol (74 vs 78 ng/ml; P < 0.05) and t-PA antigen (4.3 vs 4.5 ng/ml; P < 0.05) were lower after than before the Strauss waltz. The muscle by Henze lowered the concentrations of cortisol (70 vs 84 ng/ml; P < 0.05), noradrenaline (203 vs 224 ng/l; P < 0.05) and t-PA antigen (4.1 vs 4.6 ng/ml; P < 0.05). After listening to the piece by Shankar the concentrations of cortisol (71 vs 78 ng/ml; P < 0.05), adrenaline 14.5 vs 24.5 ng/ml; P < 0.05) and t-PA antigen (4.2 vs 4.3 ng/ml; P < 0.05) were lower. In healthy subjects AFF (29 vs 26%; P < 0.05) rose after the Strauss music, VTI-E fell (69 vs 73 mm; P < 0.05, while natriuretic peptide rose (63 vs 60 pg/ml; P < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Stress reduction through listening to music: effects on stress hormones, hemodynamics and mental state in patients with arterial hypertension and in healthy persons]. 778 98

In the present study, we demonstrate that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) interact with angiotensin II (Ang II) in regulative blood coagulation and fibrinolysis by suppressing the expressions of both tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by Ang II. The expressions of TF and PAI-1 mRNA were analyzed by northern blotting methods, and the activities of TF on the surface of rat aortic endothelial cells (RAECs) and PAI-1 in the culture media were respectively measured by chromogenic assay. Both BNP and CNP suppressed the expressions of TF and PAI-1 mRNA induced by Ang II in a time- and concentration-dependent manner via cGMP cascade, which suppressions were accompanied by respective decrease in activities of TF and PAI-1. However, neither the expression of tissue factor pathway inhibitor (TFPI) nor tissue-type plasminogen activator (TPA) mRNA was affected by the treatment of BNP and CNP.
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PMID:Natriuretic peptides regulate the expression of tissue factor and PAI-1 in endothelial cells. 1059 44

Brain natriuretic peptide (BNP) gene expression accompanies cardiac hypertrophy and heart failure. The vasoconstrictor endothelin-1 (ET) may be involved in the development of these diseases. ET has also been shown to activate phospholipase A(2) (PLA(2)), and the resulting metabolites are important second messengers. We studied how ET and PLA(2) metabolites regulate BNP gene expression. The human BNP (hBNP) promoter (from -1818 to +100) coupled to a luciferase reporter gene was transferred into neonatal ventricular myocytes (NVMs), and luciferase activity was measured as an index of promoter activity. ET induced BNP mRNA in NVMs as assessed by Northern blot. It also stimulated the hBNP promoter, an effect completely inhibited by actinomycin D. To test the involvement of different PLA(2) isoforms, transfected cells were treated with various PLA(2) inhibitors before stimulation with ET. Only Ca(2+)-independent PLA(2) blockade prevented ET-stimulated hBNP promoter activity. The PLA(2) metabolite lysophosphatidic acid (LPA) also activated the hBNP promoter, but arachidonic acid itself did not. ET regulation of the hBNP promoter is pertussis toxin-sensitive. The nonreceptor tyrosine kinase Src and the small GTPase Rac mediate the effects of both ET and LPA in stimulation of the hBNP promoter. We studied the involvement of cis elements in ET-stimulated hBNP promoter activity. Deletion of BNP promoter sequences from -1818 to -408 and from -408 to -40 reduced the effect of ET by 60% and 80%, respectively. Moreover, ET-stimulated luciferase activity was reduced by 50% when the proximal GATA element was mutated. These data suggest that (1) ET activates the hBNP promoter through a transcriptional mechanism; (2) LPA, perhaps generated by iPLA(2), is involved in the effect of ET; (3) Src and Rac mediate ET and LPA stimulation of the hBNP promoter; and (4) ET regulation of the hBNP promoter targets both distal and proximal cis elements.
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PMID:Src and Rac mediate endothelin-1 and lysophosphatidic acid stimulation of the human brain natriuretic peptide promoter. 1123 Mar 22

More than thirty years have passed since streptokinase was first shown to dissolve pulmonary arterial thrombi and normalize pulmonary artery pressure in patients with acute pulmonary embolism (PE). Following the initial observations, a number of controlled clinical trials confirmed that treatment with streptokinase, urokinase or alteplase recombinant tissue plasminogen activator is superior to heparin alone in improving angiographic and hemodynamic parameters in these patients. At present, there is consensus that patients with massive PE presenting with overt right ventricular failure (clinical instability and cardiogenic shock) should promptly be treated with thrombolytic agents, since they are at a particularly high risk for death or life-threatening complications during the acute phase. At the other end of the clinical spectrum, thrombolysis for PE is not indicated in the absence of right ventricular dysfunction. In fact, the prognosis of patients with small pulmonary emboli (not affecting pulmonary artery pressure and right ventricular afterload), is excellent and, as a result, the bleeding risks of thrombolysis may outweigh the potential benefits of this treatment. Currently, the thrombolysis debate focuses on patients with submassive PE, i.e. those who present with signs of subclinical, impending right heart failure. Recently, a number of clinical studies demonstrated that these patients are also at risk for an adverse clinical outcome. Besides the established prognostic value of echocardiography, evidence is now accumulating that cardiac troponins and, possibly, pro-brain natriuretic peptide levels also may permit an early, reliable risk stratification of patients with PE and particularly help identify submassive PE in the presence of apparent clinical stability. Recently, the Management Strategies and Prognosis of Pulmonary Embolism-3 trial examined the effects of thrombolysis on the prognosis of patients with acute submassive PE. The study patients were randomly assigned to receive alteplase (100 mg over 2 hours) or placebo with concomitant heparin anticoagulation. Although in-hospital mortality was low in both the alteplase and the heparin-only group, this study showed for the first time that early treatment with alteplase can improve the clinical course of patients with acute submassive PE, and particularly reduce the need for emergency escalation of treatment. Importantly, no fatal or cerebral bleeding episodes were observed in the alteplase group. This fact indicates that use of thrombolysis in PE can be safe in patients who have no contraindications to this type of treatment. Based on these data, the indications for thrombolysis can be extended to include patients presenting with submassive PE.
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PMID:Should thrombolytic therapy be used in patients with pulmonary embolism? 1504 19

We investigated the efficacy and safety of extended enoxaparin monotherapy in symptomatic patients with acute pulmonary embolism (PE). We randomized 40 patients in a 1:1 allocation to enoxaparin monotherapy (1 mg/kg twice daily for 10-18 days, and then 1.5mg/kg once daily until day 90) (n = 20) or to enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin with a target international normalized ratio of 2.0-3.0 for 90 days (at least 10 doses of enoxaparin overlapping with warfarin for at least 4 days) (n = 20). All patients underwent echocardiography, cardiac troponin I (TnI), and brain natriuretic peptide testing to identify patients with an increased likelihood of adverse clinical outcomes. The end-points were newly diagnosed deep venous thrombosis (DVT) or PE and bleeding events through day 90. In 15 patients on extended enoxaparin therapy, we used repeated measure analysis of variance (ANOVA) to investigate differences in anti-Xa levels obtained at 2, 4, 8 and 12 weeks. The patients' mean age was 52 +/- 17 years; the most common comorbidities were obesity (58%), hypertension (30%), concomitant DVT (30%) and cancer (15%). Twelve (30%) patients had elevated cardiac Tnl >0.1 mg/l and 11 (28%) had moderate or severe right ventricular dysfunction on echocardiography. Ten (25%) patients received thrombolysis with a continuous infusion of 100 mg alteplase prior to randomization. During a 90-day follow-up, one patient from the enoxaparin monotherapy group suffered symptomatic distal DVT; one from the warfarin group had recurrent symptomatic PE (p = 1.0). None of the study patients had major hemorrhage; two warfarin group patients had minor bleeding compared with none in the enoxaparin monotherapy group (p = 0.49). Repeated measure ANOVA did not reveal significant differences in anti-Xa levels over time (p = 0.217). In patients with acute symptomatic PE, extended enoxaparin monotherapy is feasible and warrants further investigation in a large clinical trial.
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PMID:Extended enoxaparin monotherapy for acute symptomatic pulmonary embolism. 1644 53

This study aimed to characterize matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in relation to changes in left ventricle (LV) geometry and function in a porcine model with streptozotocin (STZ)-induced diabetes. In 15 Chinese Guizhou minipigs with STZ-induced diabetes (diabetic group) and 15 age-matched normal controls (control group), Doppler tissue imaging was performed at 6 months of diabetes. Serum MMP-2, -9, TIMP-1, -4 and B-type natriuretic peptide (BNP) were determined. Expression of MMPs, TIMPs, urokinase type-plasminogen activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in aortic intima and LV myocardium was evaluated, with gelatinolytic activities of tissue MMP-2, -9 accessed by zymography. Left ventricle end-diastolic septum thickness (P < 0.05) and mass (P < 0.05) were increased, whereas peak systolic mitral annulus velocity (Sm, P < 0.001), LV systolic (P = 0.01) and diastolic strain (P < 0.001) were significantly decreased in diabetic group than in controls. Diabetic group showed higher expression of TIMP-1, -4 in aortic intima and LV myocardium (P < 0.01 or P < 0.05), with increased collagen content and elevated serum BNP level (P = 0.004) and lower gelatinolytic activities of tissue MMP-2, -9 (all P < 0.05). Semi-quantitative RT-PCR of those diabetic tissues revealed elevated mRNA levels of major TIMPs, uPA, uPAR and PAI-1. Reduction of serum MMP-2 and -9 levels was observed in diabetic group vs. control group (both P < 0.05). This study features elevated levels of TIMP-1, -4, uPA, uPAR and PAI-1, and decreased activities of MMP-2, -9 in aorta and myocardium in STZ-induced diabetic minipigs, indicating that MMP-TIMP dysregulation is associated with LV hypertrophy, cardiac dysfunction and increased cardiovascular fibrosis in diabetes.
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PMID:Dysregulation of matrix metalloproteinases and their tissue inhibitors is related to abnormality of left ventricular geometry and function in streptozotocin-induced diabetic minipigs. 1833 30

Diabetic cardiomyopathy can progress toward overt heart failure with increased mortality. The hexosamine biosynthesis pathway has been implicated in signaling for fibrosis by the kidney. Thiamine (vitamin B(1)) is an indispensable coenzyme and required at intracellular glucose metabolism. In this study, we assessed if decrease of flux through the hexosamine biosynthesis pathway induced by high-dose thiamine therapy counteracts diabetes-induced cardiac fibrosis. The diabetes model used was the streptozotocin-induced diabetic rat. Normal control and diabetic rats were studied for 2 weeks with and without thiamine, and followings were analyzed; plasma biochemicals (total cholesterol and triglycerides), morphological changes, mRNA abundance relevant to cardiac failure (brain natriuretic peptide) and fibrosis (transforming growth factor-beta1, thrombospondine, fibronectin, plasminogen activator-I and connective tissue growth factor) as well as and matrix metalloproteinase activity were investigated. Thiamine repletion prevented diabetes-induced cardiac fibrosis without changes in plasma glucose concentration. This was achieved by prevention of thiamine depletion, increased pro-fibrotic mRNA abundance and decreased metalloproteinase activity in the heart of diabetic rats. O-glycosylated protein was significantly higher in the left ventricular of diabetic rats compared to control rats, which was decreased by thiamine administration. Thiamine repletion prevented diabetes-induced cardiac fibrosis in experimental diabetes, probably by suppression of hexosamine biosynthesis pathway.
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PMID:Prevention of incipient diabetic cardiomyopathy by high-dose thiamine. 1882 45

Von Willebrand factor (VWF) and tissue plasminogen activator (t-PA) predict adverse cardiovascular outcome following acute myocardial infarction (AMI) and are weakly associated with pre-discharge left ventricular ejection fraction (LVEF). We examined the relationships between VWF, t-PA antigen, matrix metalloproteinase (MMP)-2,-3, and -9, and B-type natriuretic peptide (BNP), and their predictive effect on serial change in LV volumes in a cohort of patients admitted with AMI. Plasma VWF, t-PA antigen, MMP-2,-3,-9, and BNP were measured at a mean 46 h after AMI in 100 patients (mean age 58.9 +/- 12 years, 77% male) with depressed LVEF. Cardiac magnetic resonance (CMR) imaging was then performed. Biomarker measurement and CMR were repeated at 12 and 24 weeks. Plasma concentrations of VWF, BNP and MMP-9 were elevated while t-PA antigen concentration was at the upper limits of normal; over 24 weeks VWF, t-PA antigen, MMP-9 and BNP decreased significantly. Baseline VWF correlated with BNP (r = 0.35, P < 0.001) and MMP-3 (r = 0.24, P = 0.019) as did t-PA antigen (r = 0.27, P = 0.007 for BNP; r = 0.40, P < 0.001 for MMP-3). t-PA antigen, VWF, MMP-3 and BNP were univariate predictors of LV end-systolic volume at 24 weeks; tPA antigen and BNP remained significant independent predictors on multivariate analysis. t-PA antigen and VWF are related to medium-term LV volumes after AMI, and to MMP-3. This novel link between the coagulation-fibrinolysis system and matrix turnover merits further study in understanding the pathophysiology of adverse ventricular remodeling after AMI.
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PMID:Tissue plasminogen activator antigen predicts medium-term left ventricular end-systolic volume after acute myocardial infarction. 1966 37

The growing knowledge about genetic influence on cardiovascular diseases (CVD) combined with the recently generated amounts of genomic data hold promise to the identification of new markers for atherosclerotic CVD. Cardiovascular pharmacogenomics and pharmacogenetics have now the potential for leading to identification of genetic contributors and therefore to the development of predictive genetic tests that could optimize drugs efficacy and minimize toxicity. Clinical studies have shown that genetic variations within cytochromes P450 (CYPs), 3-Hydroxyl-3-Methylglutaryl Coenzyme A Reductase (HMGCR) and apolipoprotein E (APOE) genes influence individual's response to lipid lowering statins. Furthermore, development of antagonists or inhibitors of molecules such as peroxisome proliferator-activated receptors (PPARs), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), angiotensin-converting enzyme (ACE), angiotensin receptors and tumor necrosis factor (TNF)-alpha could be another alternative to prevent atherosclerosis. In addition, novel molecules under the name of biologics including family of peptides such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), urocortin, apelin and antimicrobial peptides (AMPs) could be considered as new targets for the prevention and treatment of CVD. In this article, we will focus mainly on recent genomic advances in the development of new markers and therapeutic agents for CVD. We present an array of molecules that could have pharmacological benefit for the treatment of heart disease. We also discuss in details new strategies including biologics, which are actually the focus of companies for clinical development of therapeutic drugs. All these efforts provide optimism and attractive promise to cure CVD.
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PMID:Genomics and the prospects of existing and emerging therapeutics for cardiovascular diseases. 1975 91

The venom proteomes of populations of the highly venomous taipan snake, Oxyuranus scutellatus, from Australia and Papua New Guinea (PNG), were characterized by reverse-phase HPLC fractionation, followed by analysis of chromatographic fractions by SDS-PAGE, N-terminal sequencing, MALDI-TOF mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of tryptic peptides. Proteins belonging to the following seven protein families were identified in the two venoms: phospholipase A(2) (PLA(2)), Kunitz-type inhibitor, metalloproteinase (SVMP), three-finger toxin (3FTx), serine proteinase, cysteine-rich secretory proteins (CRISP), and coagulation factor V-like protein. In addition, C-type lectin/lectin-like protein and venom natriuretic peptide were identified in the venom of specimens from PNG. PLA(2)s comprised more than 65% of the venoms of these two populations. Antivenoms generated against the venoms of these populations showed a pattern of cross-neutralization, corroborating the immunological kinship of these venoms. Toxicity experiments performed in mice suggest that, at low venom doses, neurotoxicity leading to respiratory paralysis represents the predominant mechanism of prey immobilization and death. However, at high doses, such as those injected in natural bites, intravascular thrombosis due to the action of the prothrombin activator may constitute a potent and very rapid mechanism for killing prey.
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PMID:Comparative proteomic analysis of the venom of the taipan snake, Oxyuranus scutellatus, from Papua New Guinea and Australia: role of neurotoxic and procoagulant effects in venom toxicity. 2226 84


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