Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In diabetics, irrespective of age at onset and standing of the disease, the fibrinolytic activity in the blood is decreased, most markedly in obese patients and in those with angiopathy. In this investigation we found--significantly more often than in controls--a low release of the plasminogen activator to the blood from the endothelial cells, and also in one fourth of the diabetics an abnormally low activator activity of the vessel walls. These changes, as well as the significantly elevated levels of inhibitors of the fibrinolytic activity, will impair removal of fibrin deposits and possibly contribute to the development of vascular lesions.
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PMID:On fibrinolysis in diabetes mellitus. 5 86

The defibrinating agent ancrod has had limited clinical trial, but appears to give no advantages over heparin. Intravenous infusion of dextran, a glucose polymer, has been shown to have an antithrombotic effect in many experimental models of thrombosis. However, the evidence that dextran is a clinically valuable antithrombotic drug is conflicting. A number of controlled randomized studies have shown that dextran can prevent postoperative venous thromboembolism when a large volume of dextran 40 or 70 was infused rapidly during and after surgery. However, blood volume expansion during dextran treatment prohibits its use in patients with reduced cardiac reserve, and infrequent though sometimes severe, allergic reactions have been reported. Evidence that dextran is of value for the treatment of venous or arterial thromboembolism comes from uncontrolled studies and is not convincing. Many compounds have been shown to inhibit platelet function in vitro but only five of these drugs have been extensively evaluated as prophylactic or therapeutic antithrombotic agents in man. These are aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine and clofibrate. They have been evaluated mainly in patients with cerebral vascular disorders, coronary artery disease, peripheral artery ischaemia, venous thromboembolism, prosthetic heart valves, and in patients with arteriovenous shunts. The evaluation of the clinical effect of the platelet function suppressing drugs is in its early stages, but they appear to differ from each other in the spectrum of their clinical effectiveness, and they may be more effective in arterial than in venous thromboembolic disorders. Their role in the management of cerebral vascular disease and coronary artery disease is still uncertain, and should be clarified by the results of a number of multi-centre, prospective, randomized studies which are currently in progress. Three types of thrombolytic drugs have been evaluated clinically; the plasminogen activators streptokinase and urokinase, proteolytic enzymes such as plasmin, and agents which increase the level of endogenous plasminogen activator (e.g. anabolic steroids). Of these, the plasminogen activators now have a definite place in clinical practice. The plasminogen activators accelerate the lysis of recent venous thrombi and pulmonary emboli, and of arterial thrombi or emboli. Thrombolytic therapy with these agents should be considered particularly in patients with recent major pulmonary embolism, as lysis of recent emboli is rapid and substantial. It should also be considered in patients with recent extensive venous thrombosis, because total lysis of venous thrombi has been reported to result in long-term preservation of valve function, and is likely to prevent postphlebitic syndrome, though this has not been proven. However, plasminogen activator therapy carries a higher risk of bleeding than heparin treatment...
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PMID:Antithrombotic drugs: part II. 78 6

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria. 162 64

Endoglycan, a heparan-dermatan sulphate association, is a highly purified heparinoid extracted from porcine intestinal mucosa. The aim of our study was to investigate the fibrinolytic system in a group of healthy controls and vascular disease patients, before and after endoglycan administration "per os". All the patients had a reduced basal fibrinolytic activity. The tests carried out were PT, PTT, FDP, Euglobulin Lysis Time (ELT), fibrinogen, plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin and t-PA activity assayed with a chromogenic method. After endoglycan administration, we have shown a significant shortening of ELT with complete normalization during the treatment. A fibrinogen decrease and either plasminogen or alpha 2-antiplasmin increase was seen. This was shown in normals too, however to a lesser extent. During therapy most of the healthy subjects, but only some patients, showed increased t-PA levels. Before and during treatment, significantly higher t-PA levels were seen in the control group as compared to the patients group. Reduced t-PA release was seen in our vascular disease patients. In conclusion, endoglycan "per os" appears to exert a stimulatory effect on the fibrinolytic system.
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PMID:Fibrinolytic effect of a particular glycosaminoglycan (endoglycan) per os on normals and in patients with chronic artery disease. 170 5

Impaired function of the fibrinolytic system might be involved in the development of vascular disease and thromboembolic complications in diabetic patients. We studied kinetics of plasmin formation using t-PA and Pg purified from the plasma of three individual uncontrolled type I diabetic patients. Activation of diabetic Pg by normal t-PA in the presence of stimulating CNBr fragments of fibrinogen exhibited a prolonged lag phase (30 to 60 minutes) until maximally stimulated plasmin formation occurred (normal, 5 to 15 minutes) and substrate inhibition at Pg concentrations more than 10 to 30 nM. When normal Pg was activated by diabetic t-PA in the presence of CNBr-f, differentiation between lag phase and phase of maximal plasmin formation was not possible (activation time was 2 hours) and a high Km (7.5 microM) was calculated. After normalization of metabolic parameters in the patients studied, functional properties of t-PA and Pg improved. Km of diabetic t-PA returned to normal values (0.02 to 0.09 microM) and for diabetic Pg the prolonged lag phase was shortened, indicating that the functional abnormalities were reversible and possibly caused by metabolically induced changes (such as nonenzymatic glucosylation) in the t-PA or plasminogen molecule. We also studied the effect of in vitro glucosylation on functional properties of Pg. Similar, but less pronounced substrate inhibition as with diabetic Pg was observed when this glucosylated Pg was activated by t-PA in a system stimulated by CNBr fragments of fibrinogen. Therefore nonenzymatic glucosylation might explain, at least in part, functional abnormalities observed with Pg from diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasminogen activation in diabetes mellitus: kinetics of plasmin formation with plasminogen and tissue plasminogen activator from diabetic donors. 183 61

The pathogenesis of diabetic vasculopathy has been related to modifications in hemostasis and fibrinolysis. 50 non insulin dependent diabetes mellitus patients have been studied. Euglobulin clot lysis time, fibrin plate, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, Protein C and S, cholesterol, triglycerides and Hb A1c were determined in blood samples. Diabetic patients showed decreased fibrinolytic activity, as measured by ECLT, with clearly increased PAI levels. Fibrinolytic response to venous occlusion was lower than normal. Vascular complications were associated both with an even higher PAI activity and with a decreased fibrinolytic response to venous occlusion. Elevated PAI activity and decreased fibrinolytic response to stimulus may contribute to vascular disease in diabetes.
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PMID:Hypofibrinolysis associated with vasculopathy in non insulin dependent diabetes mellitus. 211 76

The balance between proteases and antiproteases in the lower respiratory tract is believed to play a role in the outcome of interstitial lung diseases. In this cross-sectional study, we measure several phagocyte derived enzymes, namely plasminogen activator, neutrophil elastase and an ill-defined protease active on the trialanine chromophore substrate succinyl-alanine3-nitroanilide (SLAPN) in bronchoalveolar lavage (BAL) fluid from 42 patients with pulmonary sarcoidosis and from 43 patients with collagen vascular disease (CVD), 22 without lung disease (group I) and 21 associated with parenchymal lung disease (group II). The results show: a) that sarcoidosis is associated with increased plasminogen activator activity and with the presence of enzymatic activity against SLAPN corresponding at least in part to a metalloprotease; b) that CVD in the absence of radiographic lung disease is associated with an increase of plasminogen activator activity and increased levels of alpha 1-antiprotease-neutrophil elastase complexes; c) that the majority of untreated CVD (group II) patients have detectable levels of neutrophil elastase activity. These data show that patients with pulmonary sarcoidosis and CVD have different enzymatic profiles in their lower respiratory tract as assessed by BAL. Thus, sarcoidosis (mostly lymphocytic) is associated with enhanced macrophage-derived proteolytic activity in BAL, while CVD patients both with and without lung disease have increased neutrophil counts and neutrophil elastase complexed to alpha 1-protease inhibitor and presumably inactive in BAL. Finally, only BAL from untreated CVD patients with interstitial lung disease contain neutrophil elastase activity. This latter activity could contribute to the lung lesions frequently observed in these disorders.
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PMID:Phagocyte enzymes in bronchoalveolar lavage from patients with pulmonary sarcoidosis and collagen vascular disorders. 218 5

The accumulated body of evidence suggests a role for a cell-mediated immune mechanism in the pathogenesis of scleroderma vascular disease. The most likely target for immune injury is either the endothelial cell itself or components of its basal lamina, which include type IV collagen and laminin. Whatever the specific target, the net effect is persistently altered endothelial cell dysfunction. However, the molecular basis for the development of endothelial cell injury is not known. Direct investigations of perivascular infiltrating cells have not been possible yet; published studies have focused on the in vitro effects of peripheral blood mononuclear cells and selected cytokines on endothelial cell behavior and function. Understanding the multiple cellular effects of various cytokines on endothelial cells may further the knowledge of the vascular disease. Systematic study of interactions between endothelial cells and cells of the immune system may provide the molecular basis for vascular injury and open yet unidentified avenues for therapy. Furthermore, monitoring parameters of endothelial cell injury may help to define the disease in an earlier and more meaningful fashion. Circulating levels of EC products such as von Willebrand factor, plasminogen activator, and prostacyclin/thromboxane metabolites may permit a precise definition of disease activity and assist the clinician in monitoring responses to therapy.
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PMID:Vascular disease in scleroderma. Endothelial T lymphocyte-fibroblast interactions. 240 11

Impairment of the release of plasminogen activator has been looked for in patients with a predisposition to vascular disease or venous thrombosis. In normal people the fibrinolytic activity of the blood rises sharply after strenuous physical exercise or after the administration of certain drugs, among which DDAVP. These measures fail to elicit a normal response in many of these patients. In most cases this turned out to be due to a high level of a circulating plasminogen activator inhibitor which suppresses the rise in fibrinolytic activity. Release of activator can only be demonstrated reliably by the assay of t-PA-antigen. An impaired release appears to be very rare and in the experience of the author it occurs with some regularity only in patients with terminal renal insufficiency.
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PMID:[Disorders in the release of plasminogen activators]. 242 2

Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of fibrinolysis. It circulates in blood both in free active form and in inactive form complexed with tissue type plasminogen activator (t-PA). Control mechanisms for its synthesis and release from hepatocytes and endothelial cells are important in the pathogenesis of thrombosis. Possible risk factors for myocardial infarction include high insulin and PAI-1 levels, which correlate with one another in healthy subjects, and fibrinogen, which together with PAI-1, is an acute-phase reactant. We therefore studied the interrelationships between PAI-1, plasma insulin, and acute-phase proteins in 67 patients with angina pectoris. Plasma insulin correlated strongly (r = 0.59, p less than 0.001) with PAI activity, free PAI-1 antigen (r = 0.60, p less than 0.001), and total PAI-1 antigen (r = 0.58, p less than 0.001). The acute-phase proteins, fibrinogen and C-reactive protein, correlated significantly with t-PA antigen, total PAI-1 antigen, and PAI-1/t-PA complexes but not with PAI activity or free PAI-1. The results suggest that insulin stimulates synthesis and release of free PAI-1 (probably via hepatocytes as previously shown with cell culture) and that endothelial cell synthesis and release of t-PA, together with PAI-1, reflects a nonspecific acute-phase response to chronic vascular disease. Hyperinsulinemia found in patients with angina pectoris could play a role in the development of myocardial infarction via the induction of high plasma PAI-1 activity.
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PMID:Plasma plasminogen activator inhibitor-1 in angina pectoris. Influence of plasma insulin and acute-phase response. 247 Mar 43


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