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)

Diabetes mellitus (DM) is associated with an increased incidence of vascular complications. Abnormalities in the hemostatic system contribute at least in part to the development of vascular disease or atherosclerosis. In order to assess the actual degree of activation of the coagulation and fibrinolytic systems in diabetics, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP) were measured together with tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 18 patients with DM (three patients with type I DM and 15 with type II DM). Mean plasma levels of TAT (2.5 +/- SD 1.2 ng/mL) and PAP (0.9 +/- 1.2 micrograms/mL) were significantly elevated in diabetics as compared with healthy subjects (1.7 +/- 0.3 ng TAT and 0.2 +/- 0.1 micrograms PAP per mL of plasma; p = 0.009 and 0.02, respectively). Plasma antigen concentration of t-PA but not of PAI-1 was also elevated. No difference was found in the levels of these variables between type I and type II diabetics or between patients with and without retinopathy or nephropathy. These findings indicate that continuous activation of coagulation and fibrinolysis actually occurs in the majority of the patients with DM.
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PMID:Activation of blood coagulation and fibrinolysis in diabetes mellitus: evaluation by plasma levels of thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex. 238 33

An increase in plasma fibrinogen content and a decrease in level of antithrombin III in plasma with ageing may cause a thrombotic tendency in the elderly, although the main cause of thrombosis in the aged is atherosclerotic change seen in these subjects. Coagulability of blood is maintained in the so-called therapeutic range in aged patients receiving oral anticoagulant, as well as in younger subjects, however, it has been pointed out that there is an increasing risk of hemorrhage, especially of intracranial hemorrhage, with advancing age. Intracranial hemorrhage is not necessarily a rare complication of anti-platelet or thrombolytic therapy in the aged. Another hazard of aspirin therapy in the aged is the abrupt development of peptic ulcer. The authors administered 40 mg of aspirin per day to ten volunteers. In these subjects, platelets in the venous blood taken in a glass tube were strongly stimulated by coagulating whole blood in the tube for 60 minutes at 37 degrees C. Under this condition, arachidonic acid in platelets was converted to thromboxane B2, which is a stable metabolite of thromboxane A2 that causes platelet aggregation and vasoconstriction to accelerate thrombus formation. After ingestion of the minidose aspirin for one week, the concentration of thromboxane B2 in the serum (not in the plasma) of the volunteers decreased to 7% of the values determined before the administration of the drug, because of inhibition of cyclo-oxygenase in the platelets by aspirin. However, concentration of 6-keto-PGF1 alpha, which is a stable metabolite of prostacyclin that originates from arachidonic acid by cyclo-oxygenase in the vessel wall, did not markedly decrease after the treatment with aspi2+ t-PA and hybrid of t-PA and scu-PA in the aged are discussed. If antithrombotic therapy is always safe in the aged, it may be rational and economical to select subjects predisposed to thrombosis among patients with atherosclerosis. Determination of levels of fibrinogen, beta-thromboglobulin and/or thrombin-antithrombin III complex in plasma may be useful to predict thrombosis.
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PMID:[Antithrombotic drugs]. 267 54

Although elevated levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with the development of myocardial infarction, the correlation between the presence of coronary artery disease and increased levels of PAI-1 is controversial. The present study evaluated the association between angiographically-documented coronary artery disease and plasma levels of PAI-1 and tissue-type plasminogen activator (t-PA) in 65 men (ages 35 to 65 years) who had no previous history of myocardial infarction, angioplasty, or other medical illnesses. PAI-1 activity in these 65 patients was inversely correlated with t-PA activity, which was measured before and after venous occlusion. PAI-1 activity correlated positively with levels of triglycerides. There was a significant negative correlation between PAI-1 activity and levels of high-density lipoprotein. Each patient was placed in one of five groups according to the severity of coronary atherosclerosis, which ranged from normal vessels (group I) to greater than 50% occlusion of three vessels (group V). There were no significant differences among the five groups with respect to mean activity of PAI-1 (p = 0.98) or t-PA activity measured before venous occlusion (p = 0.22) or after occlusion (p = 0.70). T-PA and PAI-1 activities in these five groups were not different from those in 35 healthy men. These data indicate that there is no association between activities of PAI-1 or t-PA and coronary artery disease in this well-characterized male population.
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PMID:Plasminogen activator and plasminogen activator inhibitor activities in men with coronary artery disease. 278 30

The metabolism in vitro of exogenous and endogenous arachidonic acid was studied in circulating blood monocytes obtained from control (control group) and cholesterol (0.5%)-fed (cholesterol group) rabbits. The production of superoxide anion (O2-), tissue plasminogen activator (t-PA) and adherence of monocytes were assessed in both groups of animals. The amounts of cyclooxygenase and lipoxygenase products derived from exogenously added [1-14C]AA were not significantly different in monocytes collected from both groups of animals. However, the amounts of PGD2, TXB2 and PGE2 formed from endogenous substrate were decreased significantly in monocytes obtained from the cholesterol group compared to those from the control group. The production of immunoreactive LTB4 was not suppressed significantly in monocytes collected from the cholesterol group. The production of O2- and t-PA was suppressed significantly in monocytes obtained from the cholesterol group and these cells adhered onto glass surfaces more efficiently than control cells. Since the formation of prostanoids from endogenous but not exogenous substrate is reduced, an effect of cholesterol on the liberation of AA from phospholipid pools is implicated.
Atherosclerosis 1986 Aug
PMID:Influence of cholesterol feeding on the production of eicosanoids, tissue plasminogen activator and superoxide anion (O2-) by rabbit blood monocytes. 301 60

Increased levels of an endogenous inhibitor of tissue-plasminogen activator (t-PA) have been thought to relate to the genesis of acute myocardial ischemia. To examine the role of the rapid inhibitor of t-PA, plasma samples were analyzed from 75 patients with chest pain syndrome undergoing coronary angiography (mean age 57 years), 24 patients with clinically documented coronary artery disease (unstable angina, positive exercise stress test or previous history of myocardial infarction; mean age 58 years) and 15 young normal subjects (mean age 26 years). Plasma t-PA inhibitor levels were similar in age-matched patients regardless of the absence or presence (and degree) of coronary artery disease. Plasma t-PA inhibitor levels correlated significantly with age (r - 0.46, p less than 0.005), suggesting an age-dependent decrease in fibrinolytic activity. Plasma t-PA inhibitor levels also correlated significantly with serum triglyceride levels (r - 0.60, p less than 0.001), but not with coronary risk factors such as serum cholesterol, diabetes, hypertension, serum uric acid levels or body weight. Association of high levels of inhibitor of t-PA with hypertriglyceridemia may be of importance in the development of coronary thrombosis, especially in elderly patients. Nonetheless, this study does not suggest a pathogenic role of t-PA inhibitor in coronary atherosclerosis.
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PMID:Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations. 310 May 98

Plasminogen Activator Inhibitors (PA Inhibitor) have recently been identified in plasma. They are directed against t-PA and Urokinase. Two PA Inhibitors have been described: PA Inhibitor 1 from endothelial cells, hepatocytes and platelets and PA Inhibitor 2 from placenta. Enzymatic assays have been developed. They show that plasma levels of PA Inhibitor are very low under normal conditions, but a considerable increase (X10 or 20) is found in several pathological conditions (thrombo embolic disease, atherosclerosis, thrombotic risk factors (obesity, hypertriglyceridemia, diabetes) inflammatory syndrome, post operative period for PA Inhibitor 1, and in some physiological conditions (pregnancy for PA Inhibitor 2). These results plead for a pathogenic role of PA Inhibitor 1 in the development of thrombosis. Pharmacological products able to decrease the plasma level of PA Inhibitor are as yet scarce. Stanozolol, an anabolic steroid, some biguanides such as Metformin possess this property.
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PMID:[Anti-activator inhibitors of plasminogen]. 311 99

Low fibrinolytic activity, as measured by euglobulin (EFA), has been observed in obese subjects, and hypofibrinolysis may play a role in the pathogenesis of atherosclerosis and its complications. Blood fibrinolytic activity is regulated through a complex system of activators and inhibitors, especially plasminogen activator inhibitors (PA Inhibitors). In a group of 35 non-diabetic subjects with a wide range of body mass index (BMI), EFA was negatively correlated, and PA Inhibitor activity positively correlated, with BMI and plasma insulin levels. In a population of 49 non-diabetic obese women (differing from a control group of normal weight by lower EFA and higher level, of PA Inhibitor activity, plasma insulin and triglyceride), the PA Inhibitor activity was positively correlated with BMI, insulin and triglyceride. The increase in PA Inhibitor activity was associated with a high value of PA Inhibitor 1 antigen measured by an immuno-radiometric assay, indicating that the increased activity was due to a high level of circulating PA Inhibitor 1. Plasma insulin was lowered in obese non-diabetic subjects, without modification of the body weight, by a 24 hour fast or by treatment with Metformin. After 24 hours' fast, ten obese subjects had lower levels of insulin and PA Inhibitor activity and an increase in EFA. Treatment for 15 days by 1.75 g Metformin (or placebo), on a weight maintaining diet, induced, in the Metformin group, a decrease in plasma insulin, triglyceride and PA Inhibitor activity and an increase in EFA, while no change was observed in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationships between plasma insulin triglyceride, body mass index, and plasminogen activator inhibitor 1. 311 43

Dysfunction of vascular endothelial cells and accelerated calcification of the abdominal aorta were found in patients on maintenance hemodialysis. Indicators of vascular wall function, expressed as the amount of plasminogen activator and von Willebrand factor released during venous occlusion, suggested that the cubital venous wall in patients has normo- or hyper-responsiveness to occlusion. Calcification of the abdominal aorta on CT scan image was observed in most of patients including those of the ages of twenties years. The mean aortic calcification index (ACI), as an indicator of organic changes in vascular wall, was significantly higher in dialysis patients than in the nondialysis subjects. However, the mean values of indicators for vascular wall function decreased and ACI increased, as the period of treatment with hemodialysis became longer. A significant negative correlation was found between the mean ACI and most indicators of vascular wall function. The function of cubital vein was suggested to decrease in association with the progress in mural calcification of the abdominal aorta. We conclude that the alteration of the coagulation-fibrinolysis system induced by repeated hemodialysis may result from and continue to exacerbate endothelial damage, the consequence of which may be atherosclerosis.
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PMID:Response of the cubital vein to occlusion and calcification of the abdominal aorta in patients with chronic renal failure on maintenance hemodialysis. 334 28

Impaired fibrinolysis is believed to promote atherosclerosis and contribute to myocardial infarction. The major triggering factor for fibrinolysis is vascular tissue plasminogen activator (t-PA), and the aim of this study was to evaluate the capacity of human arterial smooth muscle cells (SMC) for induction of fibrinolysis. SMC were plated on labeled fibrin gels, and lysis was measured as release of label. Fibrinolytic capacity was dependent on the phenotypic state of SMC. The "multilayered phenotype" to which SMC modulate after cellular injury had a much lower fibrinolysis-inducing capacity than the more ordinary "monolayered" SMC type. Fibrinolysis was mediated by activation of plasminogen. In long-term experiments under conditions imitating thrombolysis, platelet-derived growth factor promoted fibrinolysis indirectly by increase of SMC number, and a direct effect on cellular production of t-PA was not detected. SMC from atherosclerotic intima had a much lower capacity for induction of fibrinolysis than cells from adjacent nonatherosclerotic intima. SMC also displayed several structurally detectable interactions with the fibrin substratum, such as organization of the gel by means of extension of numerous filamentous processes and contraction and wrinkling of the gel. In conclusion, human arterial SMC in vitro induce fibrinolysis by activation of plasminogen. This capacity is dependent on phenotype and lowered for SMC from atherosclerotic intima, suggesting impairment after arterial injury and in atherosclerosis.
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PMID:Impaired fibrinolysis-inducing capacity for postinjury phenotype of cultivated human arterial and human atherosclerotic intimal smooth muscle cells. 335 71

Blood coagulation and fibrinolysis were studied at rest and during bicycle ergometry in 45 patients with angina of new onset (ANO). Fourteen chronic coronary patients and 20 subjects, free of coronary heart disease or coronary atherosclerosis, were taken as controls. Fibrinolysis tended to be depressed in resting ANO patients. Potential fibrinolysis depended on the clinical pattern of the disease and was particularly depressed in patients with severe ANO. Stress did not activate fibrinolysis in patients with vasospastic angina and high basal plasminogen activator level at rest.
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PMID:[Initial-onset stenocardia: characteristics of the blood coagulation system and fibrinolysis as reaction to physical exertion]. 341 63


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