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)

Anabolic-androgenic steroid abuse has recently been linked with acute vascular events in athletes. To date, the relationship between steroid abuse and the potential for cardiovascular disease has been considered almost exclusively in terms of lipid metabolism. However, recent reports of thrombosis in androgen abusing athletes with no evidence of atherosclerosis suggests the hypothesis that thrombosis risk in such athletes could be mediated through androgen induced abnormalities of coagulation. To determine if anabolic-androgenic steroid abuse in weight lifters is associated with an activation of the hemostatic system we studied forty-nine weight lifters recruited through advertisements. History of androgen use or abstinence was confirmed via urine assays. Plasma was assayed for clotting and fibrinolytic activity by measuring thrombin/antithrombin complexes (TAT), prothrombin fragment 1 + 1 (F1 + 2), and D-dimers (D-di); markers of the endothelial based fibrinolytic components were assayed by measuring tissue plasminogen activator antigen (t-PA Ag) and its inhibitor (PAI-1); finally, the activity of antithrombin III, protein C, and protein S were measured. Abnormally high concentrations of TAT complexes were noted in 16% of our confirmed steroid using weight lifters compared to 6% of our confirmed nonusers (P = .01). Steroid users also demonstrated abnormally high concentrations of F1 + 2 and D-dimers when compared to nonusers (44 vs. 24%, P < .001, and 9 vs. 0%, respectively). Non-steroid users were more likely to have elevated levels of t-PA Ag and PAI-1 than our steroid using weight lifters (both P < .001). The activities of antithrombin III and protein S were more likely to be higher in users compared to nonusers (22 vs. 6%, P = .005; 19 vs. 0%, respectively). Some anabolic-androgenic steroid using weight lifters have an accelerated activation of their hemostatic system as evidence by increased generation of both thrombin and plasmin. These changes could reflect a thrombotic diatheses that may contribute to vascular occlusion reported in young athletes using these drugs. The predictive value of these coagulation abnormalities in terms of risk of thrombosis to individual steroid using weight lifters or the population as a whole remains to be studied.
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PMID:Anabolic-androgenic steroid abuse in weight lifters: evidence for activation of the hemostatic system. 763 72

In this population-based case-control study, we examined the relationship between the fibrinolytic variables tissue-plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity, cardiovascular risk factors and peripheral arterial disease. Cases and controls were selected from the Edinburgh Artery Study, a random sample survey of men and women, aged 55-74 years. Mean levels of t-PA antigen and PAI activity were significantly elevated in 121 cases compared to 126 controls. The increased risks of peripheral arterial disease with increasing PAI activity and t-PA antigen levels were partly mediated by interactions with serum triglycerides, high density lipoprotein (HDL) cholesterol and cigarette smoking. For example, adjustment for triglycerides significantly reduced the odds of disease for PAI activity from 1.41 (95% confidence intervals 1.08, 1.86) to 1.24 (0.93, 1.65) and from 1.47 (1.09, 1.98) to 1.34 (0.99, 1.82) for t-PA antigen. We conclude that impaired fibrinolytic potential (raised PAI activity and t-PA antigen) is associated with peripheral atherosclerosis and that this relationship is partly influenced by lipids and cigarette smoking.
Atherosclerosis 1995 May
PMID:Tissue-plasminogen activator, plasminogen activator inhibitor and risk of peripheral arterial disease. 766 86

The plasminogen activator (PA) system may participate in the pathogenesis of atherosclerosis by modulating the turnover of intimal fibrin and extracellular matrix deposits and by contributing to intimal cell migration. We present an analysis of tissue-type PA (tPA) and urokinase-type PA (uPA) expression at three levels: mRNA by in situ hybridization, antigen by immunohistochemistry, and enzymatic activity by histoenzymology and zymography. For PA colocalization with cellular or matrix components, we used double immunofluorescence labeling in conjunction with confocal microscopy. In normal arteries, tPA antigen and mRNA were detected in endothelial cells and smooth muscle cells (SMCs). In atherosclerotic arteries, tPA antigen and mRNA were increased in intimal SMCs and in macrophage-derived foam cells of fibro-fatty lesions. Part of the tPA was detected in the extracellular space and colocalized with fibrin deposits. uPA antigen and mRNA were detected in association with the intimal macrophages and SMCs. A particularly high uPA expression was noted on macrophages localized on the rims of the necrotic core. Moreover, using a novel histoenzymological assay as well as classic zymography, we revealed uPA-dependent lytic activity in the advanced lesions, whereas in normal arteries, only tPA-dependent activity was detected, mainly over the vasa vasorum. Also, strong tPA and uPA staining was detected in neomicrovessels of the plaques, suggesting that PAs may play a role in plaque angiogenesis. Our results suggest a local dynamic process of PA-dependent proteolysis in lesion areas that is associated with macrophages and SMCs. A better comprehension of these proteolytic mechanisms in advanced atherosclerotic plaques may provide the basis for therapeutic approaches for plaque stabilization.
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PMID:Plasminogen activator expression in human atherosclerotic lesions. 767 Sep 60

D-dimer, plasminogen activator inhibitor (PAI-1) activity at rest and after exercise, and tissue plasminogen activator (t-PA) activity after exercise were measured in venous blood in 88 patients with atherosclerotic lesions of various degrees. According to clinical symptoms, coronary angiography (CAG), ultrasound Doppler signal and duplex and colour Doppler scanning of carotid arteries and their branches, subclavian, vertebral and peripheral arteries of the lower limbs, patients were divided into four groups. Group 1, 16 men without CAG and ultrasound signs of atherosclerotic lesions; group 2, 27 patients with CAG-confirmed coronary artery disease; group 3, 18 patients with peripheral artery occlusive disease; group 4, 27 patients with coexistence of two or more regions of atherosclerotic lesions. D-dimer was the highest in patients with the most extensive atherosclerosis: 432 +/- 164 ng.ml-1 in group 3, 429 +/- 98 ng.ml-1 in group 4 vs 163 +/- 25 ng.ml-1 in group 1, P < 0.05. There were correlations (P < 0.05) between: age and D-dimer (r = 0.29); D-dimer and t-PA (r = 0.34); D-dimer and PAI-1, r = -0.29. Patients were also analysed according to D-dimer level. In patients with the highest level of D-dimer, the lowest level of PAI-1 activity and the highest level of t-PA activity after exercise were observed. The low PAI-1 activity is probably the result of an increased release of t-PA in these patients.
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PMID:D-dimer and fibrinolysis in patients with various degrees of atherosclerosis. 773 19

The fibrinolytic potential of the endothelial cells gives important antithrombotic properties to the vascular wall. Thrombosis is a frequent complication to atherosclerosis and other conditions where inflammatory mediators are present in the vascular wall. Inflammatory agents like lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF alpha) have been demonstrated to modulate the expression of fibrinolytic factors in cultured endothelial cells. In the present study the expression of tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (u-PA) and plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) antigen in conditioned medium from cultured human umbilical vein (HUVEC) and human saphenous vein (HSVEC) endothelial cells was investigated under basal conditions and after stimulation with LPS, TNF alpha, interferon-gamma (IFN-gamma) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNF alpha increased the expression of PAI-1, u-PA and PAI-2 in HUVEC and HSVEC, while the t-PA response differed between the two cell types. The effects of TNF alpha were modulated by IFN-gamma but not by IL-6. The increased expression of u-PA after stimulation with TNF alpha was reduced by IFN-gamma. In contrast, TNF alpha-induced expression of PAI-2 was synergistically increased by addition of IFN-gamma. These effects of IFN-gamma represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction.
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PMID:Interferon-gamma modulates the fibrinolytic response in cultured human endothelial cells. 777 58

Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL-1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.
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PMID:Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. 778 64

We have used the photochemically induced thrombosis model to study intimal thickening in the guinea-pig femoral artery. The femoral artery was occluded by a combination of rose bengal and green light which caused endothelial cell damage followed by formation of platelet rich thrombus at the site of endothelial damage. Thrombolysis was then achieved by administration of tissue-type plasminogen activator. Intimal thickening in the femoral arteries was histologically measured at 0, 1, 3, 6 and 9 weeks after the treatment. The neointimal areas gradually increased until 3 weeks and then remained unchanged up to 9 weeks. Cells in the neointima were identified as smooth muscle cells by immunohistochemical staining with an actin-specific antibody, HHF35. Cell proliferation in the media begun within 48 h after the thrombolysis and bromodeoxyuridine labeled cells appeared to migrate to the intima within 1 week after the thrombolysis. Administration of an angiotensin converting enzyme inhibitor, cilazapril (30 mg/kg/day, p.o.) for 3 weeks, suppressed intimal thickening and decreased the medial area in the femoral artery. These observations suggest that in this model cell proliferation and migration characteristics of pathological intimal thickening occur and this model is useful for investigating the effect of pharmacological preparations on intimal thickening.
Atherosclerosis 1994 May
PMID:Experimental intimal thickening studies using the photochemically induced thrombosis model in the guinea-pig femoral artery. 794 54

We evaluated 106 subjects with and 109 subjects without a history of ischemic stroke. All were attending a metabolic ward. The two groups were compared for major risk factors for ischemic events. A positive family history for ischemic complications of atherosclerosis was more common in subjects with a history of stroke than in those without; moreover, plasma levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (TPA) were higher in patients with documented previous events. A strong positive significant correlation was found between TPA and PAI-1 levels, and an interaction between age and TPA was observed when the sample was stratified according to ages being above or below 70 years. When the patient population was analyzed according to the number of ischemic events, it was found that 62 of the 106 subjects with a history of stroke had experienced more than one ischemic event. Under these conditions, the levels of TPA and PAI-1 still correlated with the occurrence of previous ischemic episodes. As in the whole patient sample, TPA was the strongest discriminator. We conclude that in subjects attending a metabolic ward, TPA and PAI-1 levels consistently help identify subjects with a history of cerebral ischemic episodes and that TPA is the strongest discriminator.
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PMID:Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with a history of ischemic stroke. 794 98

Due to the incidence of symptomatic atherosclerosis in uremic patients, hemostasis-derived cardiovascular risk factors, basal plasma concentrations of some endothelial-derived glycoproteins and desmopressin-induced variations of endothelial-derived proteins were studied in 22 uremic patients on prolonged maintenance hemodialysis with no cardiovascular antecedent. Compared to control subjects, patients had increased predialysis hemostasis-related cardiovascular risk factors: high fibrinogen, proconvertin, and type 1 plasminogen activator inhibitor plasma concentrations; low albumin values; generally low antithrombin III values but sometimes high. They had high predialysis plasma concentrations of endothelium-derived glycoproteins: von Willebrand factor, tissue-type plasminogen activator and urokinase-type plasminogen activator, which are secreted by endothelial cells, but also soluble thrombomodulin, a marker of endothelial cell injury. The desmopressin-induced release of tissue-type plasminogen activator and of von Willebrand factor were lower than in controls. High fibrinogen, type 1 plasminogen activator inhibitor and low albumin plasma concentrations may be linked to repeated acute phase reactions associated with hemodialysis. Data concerning endothelium-related proteins are concordant with the co-existence of a chronic in vivo endothelial activation and endothelial injury in uremia. This could be linked to the initiation and progression of atherosclerosis.
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PMID:Increased cardiovascular risk factors and features of endothelial activation and dysfunction in dialyzed uremic patients. 799 2

Twenty obese subjects (Males = 8, Females = 12; average age = 39.5 +/- 2.5 years; B.M.I. = 36.2 +/- 2.5), 20 overweight subjects (Males = 8, Females = 12; average age = 38.5 +/- 2 years; B.M.I. = 28.8 +/- 0.4) and 20 non obese healthy subjects as controls, matched for sex and age (Males = 8, Females = 12; average age = 37.5 +/- 2 years; B.M.I. = 22.4 +/- 0.8) were selected. We determined: blood glucose, triglycerides, total cholesterol, HDL-cholesterol, Apolipoproteins A1 and B, Factor VII, fibrinogen and plasminogen. Before and after a venous occlusion test were also measured: t-PA Antigen, PAI activity and haematocrit. Metabolic, coagulative and fibrinolytic pathological changes were observed in overweight and obese subjects and the interaction of these risk factors may contribute to the pathogenesis of atherosclerosis vascular disease and to the high rate of thromboembolic events reported in obesity.
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PMID:Evaluation of cardiovascular risk factors in overweight and obese subjects. 807 94


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