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)

Expression of cellular procoagulant activity may be one of the more important responses to vascular injury. Because factor V, a coagulation cofactor in the prothrombinase complex, catalyzes the conversion of prothrombin to thrombin, it may be a key to understanding this response. Therefore, we have investigated the synthesis, secretion and expression of factor V by vascular smooth muscle cells, which proliferate at sites of vascular injury. Cultured aortic vascular smooth muscle cells constitutively secreted Factor V activity, as determined by a functional assay. Labeled factor V was immunoprecipitated from conditioned medium of [35S]methionine-labeled cells, indicating that the secreted factor V was synthesized by vascular smooth muscle cells. Treatment of vascular smooth muscle cells with tunicamycin prevented secretion of factor V, suggesting that its secretion was dependent on the presence of N-linked carbohydrate. Factor V activity was also expressed on the vascular smooth muscle cell surface, as indicated by the ability of cultured cells to promote factor Xa-catalyzed prothrombin activation. These data suggest that the proliferation of smooth muscle cells in response to vascular injury may be one mechanism that links vascular disease with thrombosis.
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PMID:Vascular smooth muscle cells synthesize, secrete and express coagulation factor V. 333 43

A ninhydrin positive compound (L2) from commercially available unfermented dry green tea (Thea sinesis) leaves is found to be a potent inhibitor of thrombin-stimulated thromboxane formation in rabbit whole blood. Its potency is compared with caffeine, a member of the methylxanthines family. Both caffeine and L2 inhibit thromboxane formation in whole blood in a dose dependent fashion. L2 inhibition when calculated as I50 by a dose response curve is found to be more than 40 fold stronger than caffeine as an inhibitor of thromboxane formation. A concentration of L2 as low as 50 microM, suppresses thromboxane formation (by 84%) whereas a concentration of 5000 microM is necessary to achieve the same inhibition with caffeine. The potent inhibitory effect of L2 on the TXB2 production maybe of benefit in the treatment of vascular disease.
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PMID:A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. 347 9

The possible role of Mg in the pathogenesis of vascular disease has recently received increasing attention. Accumulating evidence indicates that Mg strongly influences vascular tone and responsiveness to pressor agents and that Mg deficiency may be associated with an increased risk of hypertension. Moreover, experimental Mg deficiency produces vascular lesions with calcifications while increasing the dietary intake of Mg has been shown to prevent atheroma and thrombotic complications. The modifications of lipid metabolism during experimental Mg deficiency have been recently characterized. Severe Mg deficiency in weanling rats produces a marked hypertriglyceridemia and a decrease in the percentage of cholesterol transported by high-density lipoprotein. The decreased clearance of circulating triglycerides appears to be the major mechanism contributing to hyperlipemia. The same animals were found to have a reduced insulin response after intravenous glucose challenge and a slight reduction in heparin release lipoprotein lipase. A marked reduction in plasma activity of LCAT and a significant decrease in esterified/total plasma cholesterol ratio have also been reported. Severe Mg deficiency in weanling rats produces marked changes in the fatty acid pattern of total plasma lipids, as shown by decreased levels of stearic acid, increased of oleic acid and linoleic acid, and decreased levels of arachidonic acid. Platelets from Mg-deficient rats become more sensitive to thrombin. Such an increased sensitivity of platelets may in turn play an important role in initiating the vascular lesion as well as in thrombotic complications. In view of these experimental data in animal models, more work seems necessary in man to assess the effect of Mg on lipid metabolism and vascular disease.
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PMID:Magnesium, lipids and vascular diseases. Experimental evidence in animal models. 352 56

Urinary fpA excretion and fpA in plasma were studied in patients with peripheral artery disease, aortic aneurysm, severe coronary artery disease, acute myocardial infarction and in normal controls. Mean urinary fpA was significantly higher in all groups of patients than in normal controls whose excretion was 1.9 +/- 1.2 micrograms/24 hours (mean +/- SD). We found a good correlation between urinary fpA excretion and plasma fpA (r = 0.68, p less than 0.01, n = 81). The highest levels of urinary fpA were found in 9 patients with aortic aneurysm (11.9 +/- 6.1 micrograms/24 hours). The 10 patients with acute myocardial infarction had also abnormally elevated values (4.3 +/- 1.8 micrograms/24 hours) which were only slightly higher than the levels found in another 10 patients with myocardial infarction receiving subcutaneous heparin in a dosage of 2 X 5000 IU daily (2.9 +/- 1.7 micrograms/24 hours). The 13 patients with peripheral artery disease showed an increase in urinary fpA excretion from 4.0 +/- 1.7 to 10.5 +/- 2.3 micrograms/24 hours after percutaneous angioplasty (p less than 0.001). These data demonstrate that urinary fpA excretion may represent a valid means to detect the cumulative effect of thrombin action on fibrinogen in patients with atherosclerotic vascular disease and after therapeutic intervention.
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PMID:Fibrinopeptide A excretion in urine in patients with atherosclerotic artery disease. 402 54

Plasma and urine fibrinopeptide-A (FPA) levels were investigated in type I and II diabetic patients. Plasma FPA and 24-h urinary excretion of FPA were significantly elevated in diabetic patients compared with normal volunteers, indicating augmented thrombin activity in diabetes. Plasma and urine FPA did not differ between type I and type II diabetic subjects. Comparison of plasma FPA with blood glucose and hemoglobin A1 (HbA1) indicated that elevation of FPA is rapidly reversible and intermittent during hypo- and hyperglycemia. Although elevated plasma FPA was seen in patients of short as well as long duration of diabetes, plasma and urine FPA correlated with duration of diabetes in type I patients. In type I diabetic patients with vascular complications, hyperglycemia induced by an oral glucose challenge was accompanied by elevation of plasma FPA and acceleration of fibrinogen disappearance. These responses were not seen when the patients were treated with intravenous (i.v.) heparin before the glucose challenge. In patients without vascular complications, there was also an acceleration of fibrinogen disappearance and a marginal (not statistically significant) elevation of plasma FPA seen after the FPA response observed in vascular disease patients. In all patients, induced hyperglycemia resulted in a decrease in hematocrit and hemoglobin (blood volume expansion) and an increase in pulse pressure indicating hemodynamic changes. The association of hyperglycemia and hemodynamic changes with augmented thrombin activity is consistent with a mechanism for fibrin formation and deposition based on endothelial injury and/or increased vascular permeability. Fibrin deposition due to such a mechanism may participate in the development of the vascular complications of diabetes.
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PMID:Fibrinopeptide-A in diabetes mellitus. Relation to levels of blood glucose, fibrinogen disappearance, and hemodynamic changes. 402 10

The protein C anticoagulant pathway provides many new insights into control mechanisms for regulating coagulation. The observation that protein C deficiency is associated with thrombotic tendencies in the heterozygote (106-109) and early, lethal thrombosis in the homozygote (110, 111) points to the importance of the system as a major regulatory pathway. The complexity of the system has only recently begun to emerge. Thrombin activation of protein C at the endothelial cell surface requires not only the synthesis of thrombomodulin but the coupling of the receptor to a protein C binding site. It is reasonable to assume that an inherited or acquired deficiency in thrombomodulin might lead to thrombotic tendencies. This aspect of the system may explain, in part, the association between vascular disease and thrombosis. Once activated, protein C has an almost total dependence on protein S to express anticoagulant activity. (98) This suggests that deficiencies of protein S may also be associated with thrombotic tendencies. Protein S offers an additional intriguing property. Protein S, a regulatory protein of the coagulation system, is found both free and associated with C4BP, a regulatory protein of the complement system. The high affinity, very stable interaction between these components (85) suggests that the interaction is likely to be involved in regulation. (89) The importance of the interaction remains to be demonstrated, but clearly this is a potential direct link between major control proteins of the coagulation and complement system. Clinical studies suggest that protein C and/or thrombomodulin might be effective therapeutically. Certainly, protein C supplementation during the onset of oral anticoagulant therapy would be expected to circumvent the transient rapid decrease in protein C levels that may influence the early effectiveness of oral anticoagulants. (119) In addition to the systems clinical importance, protein C, its activation, and its function offer a variety of intriguing biochemical problems. For instance, how does thrombomodulin alter the specificity of thrombin? What is the protein C binding site on the cell surface, and what role does Factor Va or its degradation products play in the formation and regulation of this site? How does protein S facilitate activated protein C anticoagulant activity and what roles do membrane surfaces play in this system? What role does beta-hydroxyaspartic acid play in protein C activation and function? How does activated protein C influence fibrinolytic activity? The answers to these questions will undoubtedly add to our understanding of the fundamental mechanisms involved in regulating blood coagulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Protein C. 609 83

37 type 2 diabetic patients with no clinical evidence of retinopathy or vascular disease were studied at diagnosis and following control of hyperglycaemia for evidence of abnormalities of coagulation, fibrinolysis and platelet behaviour. 38% showed hyperactive platelets, demonstrating either in vitro hyperaggregability, circulating platelet aggregates, or raised plasma beta-thromboglobulin levels. 36% showed abnormally raised factor VIII coagulant activity (FVIIIc) levels, though this was mainly in female patients. The mean level of FVIIIc decreased with treatment. Anti-thrombin III (AT-III) levels were decreased, and 33% of the patients had levels less than 80%. In this group AT-III increased following treatment. No abnormalities of fibrinolysis were demonstrated. These findings support the concept that diabetes can be associated with a hypercoagulable state, which is not necessarily dependent on the presence of overt vascular disease, or correlated with the degree of chronic hyperglycaemia (HbA1c levels).
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PMID:Diabetes, a hypercoagulable state? Hemostatic variables in newly diagnosed type 2 diabetic patients. 621 31

Haemostasis was studied in 34 diabetic patients with and without detectable vascular complications (micro- and macroangiopathy). Information on platelet functions was obtained by beta-thromboglobulin determination, and of heparin-thrombin coagulation time, platelet aggregation in vivo, and on the condition of the vessel walls by estimation of factor VIII-protein (VIIIR:Ag). The results were suggestive of an increased platelet activity, the most marked abnormalities having been found in cases of angiopathy. Attention is drawn to the therapeutic possibilities offered by studies of the pathogenetic role of the abnormalities of haemostasis in diabetes.
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PMID:Haemostasis in diabetics. 623 79

A study is reported which tries to identify those members of the general population who may be at increased risk of vascular disease. It is probable that patients who have had previous thrombotic episodes are inherently more at risk of further episodes and that a thrombus many months ago will not affect current tests. Accordingly we carried out a number of tests involving platelets on 'controls', and on patients with a past history of either myocardial infarction or deep vein thrombosis (DVT) and patients suffering from intermittent claudication who also are assumed to be at higher risk than the controls. Differences were demonstrated between controls and patient groups and these differences were utilized to develop statistical functions with the ability to discriminate between the groups. The functions were then tested using a second set of data from similar groups. Those designed to discriminate between myocardial infarction patients and controls and between patients with claudication and controls were validated. The heparin thrombin clotting time was found to be the prime predictor variable; the platelet count, platelet volume, platelet factor 3 clotting time and the bleeding time have some predictive value. The antithrombin clotting time, platelet aggregation and platelet adhesiveness tests as measured were not found to have discriminating potential. It is suggested that these appropriate risk functions could be of practical value in identifying members of the general population who may be at greater risk than average. The discriminate functions for DVT patients and controls could not be validated, suggesting differences in platelet involvement in arterial and venous thrombosis.
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PMID:Platelets in the prediction of thrombotic risk. 715 92

Diabetes mellitus is a multi-component syndrome that is often complicated by angiopathy which is partly due to enhanced platelet functions. Using fluorescent dyes 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and Fura-2 AM, changes was evaluated in the concentration of baseline and thrombin-stimulated increases in intracellular ionized calcium (Ca2+i) relative to hydrogen ions in the platelets from control, insulin-treated, and non-treated diabetic rats. The cytosol of platelets from the diabetic rats were more acidic compared to the insulin-treated and normal control rats. The increased intracellular hydrogen ion concentration [H+] or decreased pH (pH) in the diabetic rat platelets is associated with an increased baseline [Ca2+]i. Upon stimulation with thrombin, the mean peak [Ca2+]i for the insulin-treated (309 +/- 97 nmol/L) and untreated (339 +/- 135 nmol/L) diabetic rats was significantly higher than the concentration for the normal rats (213 +/- 101 nmol/L). Treatment with insulin attempts to correct the diabetes-induced elevation in the baseline of [Ca2+]i and intracellular H+. These results suggest that the relationships between Ca2+ and H+ relative to binding sites are similar in the intra- and extracellular compartments. It is our conclusion that the enhanced platelet activity and associated development of vascular diseases in diabetes may be due to an increased intracellular H+ that caused an increased baseline [Ca2+]i in diabetes mellitus.
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PMID:Intracellular calcium and hydrogen ions in diabetes mellitus. 748 14


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