Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The authors report their experience in fibrinolytic therapy with Urokinase in acute myocardial infarction. There were 3 groups of treatment: 100 patients with intracoronary fibrinolytic therapy; 77 patients with peripheral venous fibrinolytic administration; 31 patients with conventional therapy. The 3 groups underwent, between 21 and 28 days after the acute event, a coronarographic examination to evaluate the persistence of patency of the vessels involved in the myocardial infarction. The short term results show that the fibrinolytic therapy (with the limitations due to the hemorrhagic complications associated with the use of Urokinase), especially via intracoronary, is significantly more useful and reliable than conventional therapy, which appears unsatisfactory. Therapeutic failures are probably due to diffuse atherosclerosis of the vessel and/or to the old age of the thrombus.
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PMID:[Fibrinolytic therapy in acute myocardial infarction. Coronarographic evaluation of short-term results]. 376 65

The capacity of macrophages to influence directly and indirectly fibrinolytic processes in atherosclerosis was studied using macrophages isolated from atherosclerotic plaques of patients undergoing surgical repair of distal aortic and femoral arteries. These cells were characterized by their morphology, adherence, esterase positivity, and expression of CD14 antigen. Production of plasminogen activator inhibitor type-1 (PAI-1) by plaque macrophages (6.7 +/- 2.7 ng/10(5) cells/24 hours [mean +/- SEM]) was significantly greater than PAI-1 production by blood monocytes isolated simultaneously from the same patients (1.8 +/- 1.5 ng/10(5) cells/24 hours). Production of tissue type plasminogen activator and urokinase type was not augmented compared to blood monocytes. Conditioned medium from cultured plaque macrophages significantly increased production of PAI-1 by endothelial cells (85 +/- 11% above basal) and vascular smooth muscle cells (25 +/- 10%) in vitro. This response was significantly greater than the response to monocyte-conditioned medium (endothelial cells 38 +/- 11%, vascular smooth muscle cells 2.5 +/- 2.0%). Stimulation of endothelial cell PAI-1 production by macrophage-conditioned medium was partially inhibitable by a monoclonal antibody to transforming growth factor-beta. Tissue type plasminogen activator production by endothelial cells and vascular smooth muscle cells was not affected by plaque macrophage- or monocyte-conditioned medium. Urokinase type plasminogen activator production by endothelial cells and vascular smooth muscle cells was undetectable in control medium and was augmented to similar levels in response to plaque macrophage- and monocyte-conditioned media. These results demonstrate upregulation of PAI-1 production by macrophages in atheromatous plaques and the capacity of soluble products from plaque macrophages to upregulate PAI-1 production by endothelial cells and vascular smooth muscle cells in vitro. These data suggest that macrophages in atherosclerotic plaques may inhibit thrombolysis both directly and indirectly by effects of their soluble products on endothelial cells and vascular smooth muscle cells.
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PMID:Atheromatous plaque macrophages produce plasminogen activator inhibitor type-1 and stimulate its production by endothelial cells and vascular smooth muscle cells. 836 83

A comprehensive study on platelet aggregation, hemostasis, fibrinolysis and serum lipids in relation to peripheral serotonergic system has been performed on 41 nephrotic patients. Enhanced platelet aggregatory responses in both whole blood and in platelet rich plasma (PRP) were found upon stimulation with different agonists when compared to healthy volunteers. Increased levels of fibrinogen, fibrin monomers, and protein C activity were observed in nephrotic patients. Euglobulin clot lysis time was significantly prolonged in nephrotic patients. Activity of tissue plasminogen activator (tPA) inhibitor was higher in nephrotic syndrome, whereas tPA activity was significantly lower in these patients when compared to controls. Urokinase concentration, lipoprotein (a), cholesterol, LDL and VLDL levels were significantly higher in nephrotic patients over controls. Whole blood serotonin was significantly lower, whereas plasma serotonin was significantly higher in nephrotic patients relative to controls. Serotonin uptake and its release from platelets were markedly diminished in patients with nephrotic syndrome. Disequilibrium in the coagulolytic system, platelet hyperactivity, hyperfibrinogenemia, disturbances in peripheral serotonergic system together with lipid abnormalities may contribute to the progression and development of atherosclerosis and an enhanced risk of thromboembolic complications in nephrotic syndrome.
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PMID:Comprehensive study on platelet function, hemostasis, fibrinolysis, peripheral serotonergic system and serum lipids in nephrotic syndrome. 911 50

Urokinase type plasminogen activator (uPA) activates plasminogen to plasmin and is often associated with diseases where tissue remodeling is essential (e.g. cancer, macular degeneration, atherosclerosis). We discuss some of the mechanisms of uPA action in diseases, and evidence that some of the early uPA inhibitors can modulate the progression of these diseases. Recently, a number of research groups have discovered, with the aid of structure-based design, a new generation of uPA inhibitors. These inhibitors are much more potent and selective than their predecessors. We will review this progress here, and give particular attention to the structural rationale associated with these observed increases in potency and selectivity.
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PMID:Inhibitors of the proteolytic activity of urokinase type plasminogen activator. 1287 Oct 64

The review summarizes data obtained by the authors and other laboratories concerning the role of urokinase plasminogen activator in vessel remodeling and angiogenesis. The data have shown that urokinase is involved in unfavorable vascular remodeling during the development of restenosis, atherosclerosis and also in the regulation of angiogenesis. Urokinase is a promising target for therapeutic interventions aimed at restenosis prevention. Urokinase gene therapy may be a perspective strategy for the treatment of tissue ischemia.
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PMID:[Plasminogen activator of urokinase-type: mechanisms of involvement in vessel remodeling and angiogenesis, gene therapy approaches to ischemia]. 1534 Oct 81

Urokinase-plasminogen activator (uPA) is a multifunctional fibrinolytic protein activating growth factors, inducing proteolytic cascades, modulating cytokines, regulating receptor shedding, cellular phenotypic modulation and protein expression. These mechanisms underlie the ability of uPA to stimulate the key processes of vascular remodelling, atherosclerosis progression, restenosis and angiogenesis, -- cell migration and proliferation. We summarized data received by us and others concerning the role of uPA in blood vessel remodelling and growth. At the present stage, the uPA may be considered as a perspective target for influences directed on both the prevention of negative arterial remodelling and restenosis as well as the stimulation of vessel growth at ischemic diseases.
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PMID:[Regulation of growth and remodeling of blood vessels: the unique role of urokinase]. 1956 22