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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is widely recognized that thrombosis is the major event in the evolution of stable vascular disease to unstable ischaemic syndromes including myocardial infarction and stroke. The purpose of this case-control study was to establish clinical and laboratory data on the possible relationship between specific components of the haemostatic system and coronary heart disease. The procoagulant activity (PCA) of peripheral monocytes and polymorphonuclear neutrophils was assessed in 21 males who had suffered a myocardial infarction (MI) and in age-matched controls. In addition, total factor VII activity, fibrinogen, tissue factor pathway inhibitor (TFPI). D-dimers, tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), tumour necrosis factor-alpha (TNF-alpha) and full blood counts were measured. Post MI patients had significantly higher monocyte PCA, higher plasma concentrations of TFPI, fibrinogen, t-PA, T/P100 and also higher total white blood cell and neutrophil counts compared to age-matched controls. This elevated procoagulant state in post MI patients could further exacerbate the disease process and increase the risk of subsequent acute ischaemic events.
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PMID:Monocyte tissue factor-like activity in post myocardial infarction patients. 969 80

Homocysteine (HC) is a highly reactive thiol intermediate in amino acid metabolism, which can modify the function of endothelial cells in a myriad of ways. In vitro, homocysteine can inhibit the thromboresistance properties of the endothelial cell by induction of procoagulant factors, inactivation of natural anticoagulant systems, and suppression of vasodilatory and platelet-modulating factors. HC also inhibits the fibrinolytic system by impairing the ability of the endothelial cell to bind tissue plasminogen activator (t-PA), by interacting directly with the t-PA binding "tail" domain of its endothelial cell receptor, annexin II. Moreover, HC influences endothelial cell gene expression as exemplified by induction of the elongation factor-1 family of polypeptides, which promote polypeptide chain elongation during mRNA translation. Induction of EF-1 subunits alpha, beta, gamma and delta by homocysteine is associated with increased turnover of at least one free thiol-containing protein, suggesting that up-regulation of these subunits may represent a mechanism for replacement of damaged or modified proteins. A more complete understanding of the diverse effects of homocysteine on endothelial cell function may provide important clues to the precise role homocysteine may play in the initiation and progression of vascular disease.
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PMID:Inhibition of endothelial cell thromboresistance by homocysteine. 1072 10

Dietary fat is known to influence the variables of blood coagulation and fibrinolysis associated with vascular disease. However, the role of fat content and/or fat composition of the diet in this regard is still not well understood. In the present study, we investigated the effects of three isoenergic diets of differing fat composition in nine healthy young men in a strictly controlled residential study. Subjects consumed the three experimental diets for periods of 2 weeks each, separated by a washout period of at least 5 weeks in a randomized crossover design. The diets provided 38% of total energy intake as fat, 45% as carbohydrate, and 17% as protein, and differed only with respect to the fatty acid composition (stearic acid-rich diet: 34.1% stearic acid, 36.6% oleic acid; oleic acid-rich diet: 65.8% oleic acid; linoleic acid-rich diet: 36.5% linoleic acid, 38% oleic acid). Blood samples were collected at the beginning and at the end of each dietary period from fasted subjects for determination of factor VII coagulant activity (FVIIc), activated factor VII (FVIIa), factor VII antigen (FVIIag), tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, fibrinogen, prothrombin fragment 1+2 (F(1+2)), and plasma lipids. There were no significant differences between diets in fasting plasma concentrations of FVIIc, FVIIa, FVIIag, fibrinogen, F(1+2), PAI-1 activity, and tPA activity. Plasma concentrations of lipids (high density lipoproteins, low density lipoproteins, triacylglycerols, and total cholesterol) were also unaffected. Although there were no changes in platelet aggregation response and membrane fluidity observed in any of the diets, increased anti-aggregatory prostaglandin E(1) binding to platelet membranes was observed only in the case of linoleic acid-rich diet. In conclusion, diets with very different fatty acid compositions, at 38% of energy as fat intake, did not significantly influence blood coagulation, fibrinolysis, or blood lipids in the fasting state in young healthy men.
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PMID:A residential study comparing the effects of diets rich in stearic acid, oleic acid, and linoleic acid on fasting blood lipids, hemostatic variables and platelets in young healthy men. 1104 36

Advanced glycolysation end products (AGEs) and the free radicals generated in this process can both be implicated in the accelerated atherosclerosis and vascular and prothrombotic microangiopathic changes typified by diabetes. The rate of formation of free radicals is dependent on the rate of protein glycosylation and therefore the level and duration of hyperglycemia. Glycation and oxidation are inextricably linked. Increased oxidative stress due to excess free radical activity may be central to diabetic vascular disease, since endothelial cell damage, lipoprotein oxidation, and modification of platelet reactivity and the arachidonic acid cascade are all properties of free radicals and their reaction products, lipid peroxides. The importance of the demonstration of the mechanism whereby hyperglycemia contributes to vascular damage opens the possibility of scavenging free radicals, which will have effects independently of improving diabetic control. Over the past 15 years, studies have shown that gliclazide not only lowers blood glucose but also confers beneficial effects on the hemorrheologic abnormalities seen in diabetic vascular disease. Clinically, gliclazide reduces platelet reactivity and stimulates endothelial prostacyclin synthesis; it also increases fibrinolysis by its effects on tissue plasminogen activator. These effects, seen both in vitro and in vivo, are independent of glycemic control and are not seen with other sulfonylureas. In clinical studies, the beneficial effects of gliclazide on platelets have been related to a reduction in oxidative stress. This property is due to gliclazide's free radical scavenging ability that relates to the unique aminoazabicyclo-octane ring grafted onto the sulfonylurea. It is fully maintained by the gliclazide modified-release preparation. In diabetes, therefore, where increased glycation and oxidation are fundamental to the pathogenesis of diabetic vascular disease, agents such as gliclazide with its antioxidant activities may have an enhanced therapeutic role.
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PMID:Vascular benefits of gliclazide beyond glycemic control. 1107 71

The influence of thyroid failure on haemostasis is controversial, both hypocoagulable and hypercoagulable states have been reported. Since both subclinical and overt hypothyroidism have been associated with atherosclerosis, a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. We investigated various haemostatic variables in 42 women with subclinical hypothyroidism and compared them to 66 euthyroid controls. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VII activity (FVII:C), factor VII antigen (FVII:Ag), factor VIII activity, von Willebrand factor (vWF), antithrombin III, heparin cofactor II, protein C, protein S, plasminogen, antiplasmin, plasminogen activator inhibitor and tissue plasminogen activator, as well as common lipid variables, were measured. Factor VII:C (P < 0.02) and the ratio FVII:C/FVII:Ag (P < 0.01) were significantly increased in subclinical hypothyroid patients compared to the control group. Both parameters remained higher in hypothyroid patients after exclusion of 18 women on oestrogen replacement therapy. No differences were found between the groups with respect to vWF or the other haemostatic and lipid variables tested. Patients with subclinical hypothyroidism had significantly higher levels of FVII:C. The greater increase in FVII:C compared to that of FVII:Ag, as shown by the increase in their ratio, might reflect the presence of activated FVIIa. This might mean a hypercoagulable state, which could contribute to the increased prevalence of coronary heart disease reported in such patients. A hypercoagulable state might be another argument in favour of thyroxine replacement treatment in subclinical hypothyroidism, especially in patients with additional risk factors for vascular disease.
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PMID:Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. 1116 51

Fibrinolytic activity has been reported to be decreased in atherosclerosis. Recently, annexin II was identified as a coreceptor on endothelial cells for plasminogen and tissue plasminogen activator. In this study, we examined whether recombinant annexin II (rAN II) protein can modulate fibrinolytic activity on vascular endothelium in vitro and in vivo. The effect of rAN II on human umbilical vein endothelial cells (HUVECs) was measured. Addition of a fluorescent plasmin substrate revealed that HUVECs treated with rAN II exhibited significantly more plasmin generation than those treated with BSA. Moreover, rAN II treatment of HUVECs restored plasmin generation impaired by plasminogen activator inhibitor-1 or homocysteine pretreatment. In a rat carotid artery thrombus model, the patency of thrombosed carotid arteries was significantly enhanced by rAN II injection, in contrast to BSA injection, without systemic blood coagulation dysregulation. We found that rAN II enhanced plasmin generation on vascular endothelium in vitro and reduced thrombus formation in vivo, and concluded that enhancement of endothelial fibrinolytic activity by annexin II could modulate the hypercoagulable state of atherosclerosis. Further study of rAN II in vitro and in vivo may lead to the establishment of novel therapeutic approaches to thrombogenic vascular disease.
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PMID:Recombinant annexin II modulates impaired fibrinolytic activity in vitro and in rat carotid artery. 1173 91

We studied the impact of cerebral amyloid angiopathy on tissue plasminogen activator-induced cerebral hemorrhages in APP23 transgenic mice. Results show that the intravenous administration of tissue plasminogen activator in APP23 mice leads to an increase in cerebral amyloid angiopathy-associated microhemorrhages and can provoke parenchymal and subarachnoidal hematomas. We conclude that cerebral amyloid angiopathy is a risk factor for cerebral hemorrhage caused by tissue plasminogen activator administration in mice and stress the need for more comprehensive studies of the relation between cerebral amyloid angiopathy and tissue plasminogen activator-induced cerebral hemorrhages in elderly and Alzheimer's disease patients.
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PMID:Thrombolysis induces cerebral hemorrhage in a mouse model of cerebral amyloid angiopathy. 1211 90

Activation of the coagulation pathway and the inhibition of the fibrinolytic pathway play a pivotal role in the pathogenesis of thrombotic vascular disease such as acute coronary syndromes. Statins have been proved to be effective in patients with acute coronary syndromes in terms of reduction of cardiovascular events. It is assumed that the direct effects on vascular cells, which are independent of lipid-lowering, particularly the alterations in coagulation and fibrinolytic pathways, may contribute to these benefits. Indeed, in endothelial cells and vascular smooth muscle cells as well as in monocytes/macrophages, stains reduce tissue factor and plasminogen activator-1 expression and activity and increase tissue plasminogen activator expression and activity. These effects are mainly mediated by the inhibition of the Rho pathway, whereas the activation of Akt by statins plays a role in the suppression of tissue factor expression. These effects on coagulation and fibrinolytic pathways may be particularly important in patients with acute coronary syndromes.
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PMID:Modulation of coagulation and fibrinolytic pathways by statins. 1269 75

Increased plasma plasminogen activator inhibitor-1 (PAI-1) has been implicated in the development of vascular disease. In type 2 diabetes mellitus high PAI-1 levels are associated with increased plasma concentrations of free fatty acids (FFA) and triacylglycerol indicating an association or a causal relationship. To answer that question, the effect of FFA/triacylglycerol on plasma PAI-1 was examined. Ten healthy male volunteers were studied for 6 h during infusion of triacylglycerol [1.5 ml/min]/heparin [0.2 IU/(kg.min)] (LIP; n=10), saline only (SAL; n=10), and saline/heparin (HEP; n=5). Plasma insulin concentrations were kept constant at approximately 35 pmol/l by intravenous somatostatin-insulin infusions and there was no significant change in plasma glucose levels during any of the study protocols. LIP increased plasma triacylglycerol and FFA approximately 3- (p < 0.001) and approximately 8- (p < 0.000001) fold, respectively, within 90 min. Baseline plasma PAI-1 measured by a bio-immunoassay was similar in HEP (11.4 +/- 2.8 ng/ml), SAL (16.6 +/- 3.6 ng/ml), and LIP studies (15.2 +/- 3.4 ng/ml). Since studies were initiated in the morning, PAI-1 decreased (p < 0.025) over time following its normal diurnal variation to 6.4 +/- 2.0 ng/ml and 4.0 +/- 2.4 ng/ml at 360 min in SAL and HEP, respectively. During LIP, however, PAI-1 increased to approximately 2.6 fold higher levels than during SAL at 360 min (16.4 +/- 4.0 ng/ml, p < 0.01). While tissue plasminogen activator (tPA) and adipsin, an adipocyte derived protease, were unaffected by LIP, changes in soluble vascular cell adhesion molecule-1 (sVCAM-1) were significantly correlated (p = 0.02) with those seen for PAI-1. This suggests that hyperlipidemia independent of insulin and plasma glucose levels stimulates vascular tissue and in turn might induce an increase in plasma PAI-1. PAI-1 then could contribute to the development of atherothrombotic vascular disease.
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PMID:Increased plasma levels of plasminogen activator inhibitor-1 and soluble vascular cell adhesion molecule after triacylglycerol infusion in man. 1295 10

Hyperhomocysteinemia is a risk factor for arterial vascular disease and venous thrombosis. The pathophysiology of this relation is unclear, but several studies suggest that hyperhomocysteinemia impairs endothelial function. We examined the effect of homocysteine lowering by B-vitamin supplementation on tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI) and von Willebrand factor (vWf)--markers of endothelial dysfunction--in hyperhomocysteinemic and normohomocysteinemic volunteers. A total of 123 healthy volunteers were randomized to placebo or B-vitamins (5 mg folic acid, 0.4 mg hydroxycobalamin and 50 mg pyridoxine) daily for 8 weeks. Before and after the intervention period, blood samples were taken for measurements of homocysteine, tPA, PAI and vWf. There was no evident association between homocysteine concentration and concentrations of markers of endothelial dysfunction at baseline. The mean reduction of homocysteine concentration was 31% (95%CI 22.7 to 39.1) in the B-vitamin group compared to 3% reduction in the placebo group. Concentrations of tPA, PAI and vWf did not change after supplementation of B-vitamins. In conclusion, the results of our study show that homocysteine reduction by B-vitamin supplementation has no effect on markers of endothelial dysfunction in healthy volunteers.
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PMID:The effect of homocysteine reduction by B-vitamin supplementation on markers of endothelial dysfunction. 1554 37


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