Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Monocyte tissue factor-like activity in post myocardial infarction patients. 969 80

The aim of our study was to estimate selected parameters of hemostasis and fibrinolysis in diabetic patients with vascular complications and obesity. The investigation was carried out in 23 type 1 diabetic subjects aged 17-56 ys, in 25 type 2 diabetic patients aged 41-69 ys and in 38 healthy persons: 16 "young"--aged 32.5 +/- 13.2 ys and 22 "old"--aged 56.2 +/- 9.4 ys. The following parameters were determined: glycaemia, HbA1c, blood level fibrinogen, euglobulin clot lysis time, plasminogen activator inhibitor (PAI-1) activity, microalbuminuria, triglyceride, total, HDL- and LDL-cholesterol concentration. Plasma fibrinogen level was elevated in type 2 diabetic subjects, and the highest concentrations were noted in patients with retinopathy or arterial hypertension, in overweight persons and--surprisingly--in type 1 diabetic subjects with nephropathy and coronary vascular disease (CVD). There were also positive correlations between fibrinogen level and systolic blood pressure (r = 0.3413, p < 0.02), diastolic blood pressure (r = 0.3809, p < 0.002) and microalbuminuria (r = 0.3552, p < 0.05). The mean euglobulin clot lysis time was prolonged in type II diabetics in comparison to the control group, especially in obese subjects. The highest activity of PAI-1 was found in overweight controls (28.87 +/- 6.24 Au/ml, p < 0.002). PAI-1 activity was also slightly increased in type 1 diabetic patients, especially with the symptoms of diabetic neuropathy, nephropathy or CHD, in comparison to the other groups. Our results seem to confirm the disturbed balance between coagulation and fibrinolysis--towards and increased risk of a prothrombotic state --in both--obese and diabetic patients--especially with advanced vascular complications.
 ...
PMID:[Some parameters of hemostasis and fibrinolysis in diabetic patients]. 1010 28

Plasminogen activator inhibitor 1 (PAI-1) is likely to play a role in vascular disease, primarily in subjects with android obesity. It has been demonstrated that PAI-1 is overexpressed in adipose tissue from obese subjects and that visceral adipose tissue produced more PAI-1 than subcutaneous fat. In the present study, the effect of insulin and glucocorticoids, which are key mediators of adipose tissue metabolism, was examined in relation to PAI-1 synthesis by human adipose tissue explants (HAT), collagenase isolated human adipocytes (IHA), cultured human stromal cells (cSC), and differentiated adipocytes from the murine clonal cell line 3T3-F442A. A significant increase in PAI-1 antigen release (1.5-fold) from HAT was detectable after 16 h of treatment with insulin concentrations of at least 10(-8) mol/l. This was associated with a PAI-1 mRNA increase. Concomitant addition of insulin (10(-8) mol/l) to forskolin (5 x 10(-5) mol/l) reversed the decrease in PAI-1 antigen caused by forskolin alone. No effect on PAI-1 antigen was observed when insulin was incubated with IHA or cSC. 3T3 F442A cells were sensitive to insulin with a four- and twofold increase in PAI-1 antigen and mRNA levels, respectively, after 16 h of stimulation with 10(-8) mol/l. Dexamethasone (DXM) significantly enhanced PAI-1 antigen and mRNA expression by HAT (1.5- and 2.5-fold increase, respectively) at concentrations of at least 10(-8) mol/l. A higher stimulation was observed with IHA (sevenfold increase) and with the differentiated 3T3 F442 cell line. Cortisol was found to be less potent than DXM. No effect was observed when glucocorticoids were incubated with cSC. Coincubation of HAT with insulin (10(-7) mol/l) and DXM (10(-7) mol/l) led to an additive effect on PAI-1 synthesis. These results support the hypothesis that PAI-1 expression in human adipose tissue is controlled by insulin and glucocorticoids and may help to explain the increase in plasma PAI-1 levels observed in patients with android obesity.
 ...
PMID:Glucocorticoids and insulin promote plasminogen activator inhibitor 1 production by human adipose tissue. 1010 8

The aim of the present study was to evaluate metabolic, coagulation and fibrinolytic parameters in 45 patients [31 men, 14 women, aged 56.5 +/- 3.5 years (mean +/- SD)] who had suffered myocardial infarction more than 6 months earlier, with or without carotid atherosclerotic lesions. After the extracranial carotid arteries had been evaluated using a B-mode Duplex scanning system, patients were subdivided into two groups: group 1 (n = 20) with carotid plaques or measurable intima-media thickness; and group 2 (n = 25) without carotid plaques or measurable intima-media thickness. Twenty-two age- and sex-matched subjects were recruited as controls (group 3). Groups 1 and 2 displayed significantly higher levels of total cholesterol, apolipoprotein B, human autoantibodies against oxidised low-density lipoprotein and the c fraction of the third component system, and significantly lower levels of high-density lipoprotein cholesterol and apolipoprotein A1 than group 3. However, serum levels of triglyceride and lipoprotein (a) were significantly higher in group 1 than in the control group. Moreover, groups 1 and 2 displayed significantly higher levels of factor VII, fibrinogen, fragment 1+2, thrombin-antithrombin complex and plasminogen activator inhibitor after venous occlusion, and significantly lower levels of tissue-type plasminogen activator after venous occlusion than group 3. Significantly higher levels of tissue-type plasminogen activator and plasminogen activator inhibitor before venous occlusion were observed in groups 1 and 2 and significantly lower levels of antithrombin III, protein C and protein S were observed in group 1 compared with the controls. Patients were also analysed according to levels of lipoprotein (a). The lowest levels of tissue-type plasminogen activator after venous occlusion and the highest levels fragment 1 + 2, the c fraction of the third component system, and plasminogen activator inhibitor after venous occlusion were observed in patients with the highest levels of lipoprotein (a). Our data demonstrate an activation of coagulation and deficient fibrinolysis in survivors of myocardial infarction, particularly in those with associated carotid atherosclerotic lesions. We speculate that this thrombophilic state may play a key role in the pathogenesis of atherosclerotic vascular disease and thromboembolic complications.
 ...
PMID:Elevated levels of lipoprotein (a) in patients suffering from myocardial infarction with carotid atherosclerotic lesions. 1049 14

Endoglin is the gene mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1), a dominantly inherited vascular disorder. Endoglin glycoprotein is a component of the transforming growth factor type beta (TGF-beta) receptor system which is highly expressed by endothelial cells, and at lower levels on fibroblasts and smooth muscle cells, suggesting the involvement of these lineages in the HHT1 vascular dysplasia. Overexpression of endoglin in mouse NCTC929 fibroblasts led to decreased migration in chemotactic and wound healing assays, as well as changes in the cellular morphology. When plated on uncoated surfaces, endoglin transfectants formed intercellular clusters, endoglin being not specifically localized to the cell-cell junctions, but homogenously distributed on the cellular surface. Although the expression of alpha5beta1 integrin and of an activation epitope of beta1 integrin were unchanged, a polyclonal antibody to alpha5beta1 integrin was able to inhibit cluster formation, suggesting the involvement of integrin ligand/s. In fact, coating with fibronectin, laminin, or an RGD-containing 80 kDa fragment of fibronectin were able to prevent the cellular clustering. Furthermore, synthesis of plasminogen activator inhibitor 1 (PAI-1), and to a weak extent that of fibronectin, were inhibited in endoglin transfectants. Thus, the presence of endoglin in mouse NCTC929 fibroblasts is associated with reduced production of certain extracellular matrix (ECM) components, which might explain their altered morphology, migration and intercellular cluster formation.
 ...
PMID:Endoglin overexpression modulates cellular morphology, migration, and adhesion of mouse fibroblasts. 1053 3

Endothelial cell injury has been implicated in the increased incidence of vascular disease associated with diabetes mellitus. In diabetic humans, elevated plasma von Willebrand Factor (vWF) has been interpreted as an indication of endothelial damage. In contrast, in an animal model of inherited insulin-dependent diabetes, the bio-breeding (BB) rat, plasma vWF levels did not differ from those in age-matched control rats during the first 7 months of diabetes although morphological evidence of mild aortic endothelial alteration or injury was observed. In the present study efforts have been made to define the endothelial alterations in BB diabetic rats compared to controls more precisely over this time period. Thus, adhesion molecules: intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) were evaluated by in situ immunohistochemistry, vWF content was determined by biochemical analysis of aortic extracts and by quantitative immunohistochemistry, plasma vWF levels were measured by ELISA and vWF mRNA by RNAse protection assay. Neither age nor diabetic state significantly affected either the expression of adhesion molecules, or the levels of circulating vWF. Endothelial vWF content was significantly increased in the diabetic vessels, as observed by both approaches but the vWF mRNA content was not different from that in control vessels. Plasma plasminogen activator inhibitor (PAI-1) activity was significantly increased in diabetic animals. In conclusion, endothelial alterations in BB rats associated with diabetes, together with the raised plasma PAI-1 levels, promote the thrombogenic potential of the vessel wall, and are consistent with an increased risk for vascular disease.
 ...
PMID:Aortic endothelial cell von Willebrand factor content, and circulating plasminogen activator inhibitor-1 are increased, but expression of endothelial leukocyte adhesion molecules is unchanged in insulin-dependent diabetic BB rats. 1072 83

Excessive oxidative stress due to hyperglycemia and glycoxidation leads to an increased production of F2-isoprostanes, one of which, 8-iso-PGF2 alpha, reaches high concentrations in plasma and urine in both insulin-dependent and non-insulin-dependent diabetics. This is associated with an increase in platelet activation, reflected by an increased urinary excretion of platelet-derived TxB2. Improved metabolic control or vitamin E supplementation reduces urinary 8-iso-PGF2 alpha and TxB2, whereas aspirin or indobufen reduces TxB2 but not 8-iso-PGF2 alpha. Since TxB2 in the urine seems to represent the common link between diabetes (as well as other risk factors) and the thrombotic complications of vascular disease, platelet activation due to lipid-glycoxidation is an important aspect in the pathogenesis of vascular complications of diabetes mellitus. Among the various plasma coagulation and fibrinolysis factors that are found to be altered in diabetes, the increased level of plasminogen activator inhibitor (PAI-1) in the plasma and in the vessel wall is of the utmost importance. Indeed, it is suspected that the atherosclerotic plaques formed in the presence of high concentrations of PAI-1 are more prone to rupture and ensuing thrombosis. The thrombosis-oriented modifications of blood platelets, coagulation and fibrinolysis are an important cause behind the high prevalence of vascular events in diabetes.
 ...
PMID:[Diabetes, coagulation and vascular events]. 1074 54

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.
 ...
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

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.
 ...
PMID:Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. 1116 51

Visceral fat accumulation often accompanies various complications, such as insulin resistance, hypertension, dyslipidemia and atherosclerosis. Adipose tissue has been found to secrete various biologically active adipocytokines including free fatty acids. Accumulation of visceral fat increases the portal free fatty acids concentration to cause insulin resistance and dyslipidemia. Tumor necrosis alpha (TNF alpha) deteriorates insulin resistance in obesity. The levels of plasminogen activator inhibitor(PAI)-1 increase and plasma adiponectin concentration decreases in obesity leading to the development of vascular disease. The finding of genes specifically expressed in visceral fat and new adipocytokines should facilitate clarification of the mechanism for the development and complications of visceral fat accumulation.
 ...
PMID:[Molecular mechanism in the development of the complications associated with obesity--the physiological and pathological role of adipocytokines]. 1126 96


<< Previous 1 2 3 4 5 6 Next >>