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)

Excessive procoagulant activity in the alveolar space may play a relevant role in the pathogenesis of pulmonary fibrosis. Hypercoagulability results from the disruption of the balance between the procoagulant and anticoagulant factors. The aim of this study was to assess the levels of molecular markers of the anticoagulant protein C (PC) pathway in the bronchoalveolar lavage fluid (BALF) and plasma of 11 patients with idiopathic pulmonary fibrosis (IPF), 14 with sarcoidosis and 16 with collagen vascular disease (CVD)-associated interstitial lung disease (CVD-ILD). Six healthy nonsmoking volunteers served as control subjects. BALF concentrations of the marker of clotting activation, thrombin- antithrombin III complex (TAT), in patients with sarcoidosis and CVD-ILD were significantly greater than those in control subjects. PC levels in BALF were markedly higher in patients with IPF (610 +/- 150 ng/ml), sarcoidosis (680 +/- 170 ng/ml), and CVD-ILD (1,580 +/- 600 ng/ml) than in control subjects (230 +/- 140 ng/ml). BALF concentrations of activated PC-PC inhibitor (APC-PCI) complex were significantly decreased in IPF (0.46 +/- 0.16 ng/ml), sarcoidosis (0. 43 +/- 0.11 ng/ml), and CVD-ILD (0.50 +/- 0.15 ng/ml) patients as compared with control subjects (1.08 +/- 0.23 ng/ml). APC-PCI/PC ratios were significantly lower in patients with IPF (2.70 +/- 1.74 ng/microg), sarcoidosis (1.94 +/- 0.82 ng/microg), and CVD-ILD (1.89 +/- 0.68 ng/microg) than in control subjects (15.91 +/- 8.45 ng/microg). Plasma levels of APC- PCI and the APC-PCI/PC ratio were also significantly decreased in patients with CVD-ILD as compared with control subjects. Overall, these findings suggest that decreased PC activation with increased procoagulant activity occurs in patients with ILD.
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PMID:Protein C anticoagulant system in patients with interstitial lung disease. 962 Sep 17

Inherited and acquired thrombophilic disorders predispose patients for thromboembolic and probably other occlusive vascular events that occur when additional risk factors play in concert. Because acute rejections in renal transplant recipients may reflect vascular events, and an impairment of the fibrinolytic system in immunosuppressed patients has been previously described, the implications of genetic or acquired risk factors of thrombophilia for the occurrence of early acute rejections after kidney transplantation were evaluated. The following risk factors of thrombophilia were determined in 97 patients after cadaveric kidney transplantation: factor V Leiden mutation, protein S, protein C, and antithrombin deficiency. In a retrospective analysis, the prevalence of acute rejections, the histologic classification when rejection episodes had been confirmed by biopsy, and other vascular complications were evaluated. In 21 of the 97 patients, an inherited or acquired risk factor of thrombophilia was detected. Prevalence of acute rejections was 71% in the first 6 mo after transplantation in patients with a thrombophilic disorder and significantly higher compared with patients without thrombophilia (41%; P = 0.017). The distribution of classic risk factors associated with acute rejections, such as number of human leukocyte antigen mismatches or percentage of panel-reactive antibodies, was similar in patients with and without thrombophilia. In the eight patients with thrombophilia and histologically proven acute rejection, four patients had an acute vascular rejection, and in two patients a vascular involvement was suspected. Furthermore, prevalence of cerebral or coronary vascular disease, or venous thromboembolic complications, was significantly higher in patients with a thrombophilic clotting defect (67%) compared with patients with normal hemostasis parameters (28%; P < 0.002). It is concluded that renal allograft recipients with thrombophilia are at risk of developing an acute rejection or other vascular event. Although the determination of thrombotic risk factors was performed at least 3 mo after an acute rejection episode, it can be presumed that acute rejection episodes are associated with subsequent coagulatory abnormalities with further consequences for transplant survival. Thus, pretransplant evaluation of genetic and acquired risk factors of thrombophilia is recommended.
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PMID:High rate of acute rejections in renal allograft recipients with thrombophilic risk factors. 964 43

Hyperhomocysteinemia is a condition which, in the absence of kidney disease, indicates a disrupted sulfur amino acid metabolism, either because of vitamin deficiency (folate, B12 and B6) or a genetic defect. Epidemiologic evidence suggests that mild hyperhomocysteinemia is associated with increased risk of arteriosclerotic disease and stroke. The relationship between hyperhomocysteinemia and thrombosis has been investigated in 10 studies involving a total of 1200 patients and 1200 controls. Eight of these studies demonstrated positive association with odds ratios that ranged from two to 13. This association was enhanced by including a methionine loading test. There is some evidence which suggests that hyperhomocysteinemia and activated protein C resistance have synergistic effect on the onset of thrombotic disease. Recent studies with animal models for mild hyperhomocysteinemia provided encouraging results in the understanding of the mechanism that underlies this relationship between mild elevations of plasma homocysteine and vascular disease. These animal models pointed to the possibility that the effect of elevated homocysteine is multifactorial, affecting both the vascular wall structure and the blood coagulation system.
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PMID:Relationship between homocysteine and thrombotic disease. 970 66

Measures of fibrinolytic and thrombotic function have been examined in 55 subjects with recently identified coronary heart disease, and age and sex matched control subjects. Measurements were particularly directed at factors and processes which could be affected by changes in endothelial function and included the euglobulin lysis time as well as plasma levels of von Willebrand factor (vWF). Plasma levels of protein S and protein C were also measured. Measurements were made before and after a period of 10-min veno-occlusion combined with rhythmic hand exercise. In addition anthropometric, haemodynamic and biochemical measurements (plasma lipids and apolipoproteins, glucose and insulin) were obtained and correlated with the haematological parameters. Protein S and vWF levels were significantly higher, both before and after veno-occlusive exercise, in subjects with CHD than in the asymptomatic controls. Euglobulin lysis times were not significantly different but only shortened on veno-occlusive exercise in those without CHD. Protein S levels were significantly correlated with systolic blood pressure, plasma total cholesterol, plasma triglyceride, plasma phospholipid, plasma fasting glucose and both apolipoprotein A1 and B levels. vWF levels were not significantly related to any of the other variables. Subjects whose pre-exercise euglobulin lysis times exceeded 6 h had significantly higher BMI, plasma total cholesterol, triglyceride, phospholipid, insulin, glucose and apoB concentrations and lower HDL cholesterol than those with lysis in less than 6 h. The findings from this study are consistent with a role for endothelial dysfunction in the production of atherosclerotic vascular disease and may indicate additional, non-haemodynamic, mechanisms for such an association. In addition, the relationship between elevated levels of protein S and CHD does not appear to depend on the demonstrated associations between protein S and a number of other cardiovascular risk factors.
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PMID:Relationships between protein C, protein S, von Willebrand factor and euglobulin lysis time and cardiovascular risk factors in subjects with and without coronary heart disease. 973 15

Coagulation is triggered during the onset of myocardial infarction, resulting in vascular occlusion. However, a causal role for individual haemostatic factors in the development of thrombotic occlusion is not established. Three cases (all relatively young women) are reported of raised factor VIII associated with myocardial infarction. Two patients presented acutely with myocardial infarction at a relatively young age with no preceding history of angina. The other patient had had venous thrombosis when young and activated protein C resistance (APCR), without the presence of factor V Leiden. A functional relation exists between APCR and factor VIII; therefore, raised factor VIII may contribute to APCR and the increased thrombotic risk in patients without factor V Leiden. Factor VIII is an important risk factor for atherothrombotic events, including sudden death, in patients with vascular disease. These cases support the association of raised factor VIII with acute thrombotic events, even in patients without significant underlying atheromatous disease.
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PMID:Raised factor VIII is associated with coronary thrombotic events. 987 27

We report a patient who had an ischemic stroke aged 22 years, an inherited type I protein C deficiency and a heterozygous genotype of prothrombin gene 20210A. In view of recent reports of an increased risk for ischemic cerebral vascular disease in patients with the prothrombin 20210A mutation, we suggest that many of the reported cases of ischemic stroke and protein C deficiency may have had additional prothrombotic disorders such as the prothrombin mutation. The current data concerning the magnified risk for stroke in patients with the prothrombin 20210A mutation suggests the need to study all patients with premature stroke for this mutation and the other risk factors for thrombosis. This would include homocysteine, lupus inhibitor, anticardiolipin antibodies, and possibly the natural inhibitors of coagulation. It is possible that patients with the prothrombin 20210A mutation and ischemic cerebral vascular disease would benefit from long-term anticoagulation therapy in a similar way to patients with the antiphospholipid syndrome.
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PMID:Ischemic stroke in a young patient with protein C deficiency and prothrombin gene mutation G20210A. 989 Jul 20

The normal aging process alters blood coagulation system in humans; this may be of great concern in the view of the known association of vascular disease with advancing age. The plasma concentration of several coagulation factors, namely fibrinogen, factor VII, factor VIII, factor IX, high molecular-weight kininogen, and prekallikrein, increase in healthy humans, paralleling the physiological aging process. Plasma parameters of clotting activation in vivo, such as prothrombin fragment 1 + 2, fibrinopeptide A, thrombin-antithrombin III complex, and D-dimer, are positively correlated with age. Nevertheless, among centenarians, biochemical signs of marked hypercoagulability are associated with a healthy state. Natural anticoagulants, including antithrombin III, heparin cofactor II, protein C, protein S, and tissue factor pathway inhibitor, can modulate the reactions of blood coagulation system. The occurrence of menopause is accompanied by a significant increase in antithrombin III plasma level; the mean antithrombin III levels in older women exceed levels in male contemporaries. In healthy elderly subjects heparin cofactor II plasma concentrations are lower than in young subjects, independently of gender. Protein C levels raise with age in both sexes, as well as free protein S levels. In women, statistically significant increases in the plasma concentration of the tissue factor pathway inhibitor have been observed, whereas no significant age-related change has been found in men. The fact that many subjects with congenital defects of natural anticoagulants do not undergo thromboembolic events in young age suggests that in healthy individuals a raise in natural anticoagulants can balance the age-related increase of procoagulant factors.
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PMID:Natural anticoagulants, aging, and thromboembolism. 995 32

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.
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PMID:Elevated levels of lipoprotein (a) in patients suffering from myocardial infarction with carotid atherosclerotic lesions. 1049 14

The effect of homocysteine-lowering treatment on thrombin generation was investigated in 17 subjects with hyperhomocysteinemia (aged 22-60 years), 11 of whom had symptomatic atherosclerotic vascular disease. All subjects had fasting total homocysteine levels above 16 micromol/L. The formation of thrombin was assessed by measuring thrombin-antithrombin III complexes and prothrombin fragment 1+2 in peripheral venous blood and in the bleeding time blood collected at 30-second intervals from skin incisions on a forearm. All the tests were performed before and after an 8-week treatment with folic acid p.o. 5 mg/day, vitamin B6 p.o. 300 mg/day, and vitamin B12 i.m. 1000 microg given on a weekly basis. Following the 8-week therapy, the median plasma homocysteine concentration became significantly reduced from 20 to 10 micromol/L, while plasma levels of fibrinogen, prothrombin, and antithrombin III as well as activity of protein C, S, and factor VII showed no changes. Vitamin treatment was associated with a significant fall in thrombin-antithrombin III complexes and prothrombin fragment 1+2 concentrations in peripheral venous blood. Bleeding time became prolonged by about 60 seconds. At sites of hemostatic plug formation, plasma concentrations of both thrombin markers significantly decreased. Compared with pretreatment values, significantly less thrombin was produced during the first 3 minutes of bleeding after homocysteine-lowering therapy. In subjects with hyperhomocysteinemia a reduction of plasma fasting homocysteine concentration by folic acid and vitamins B12 and B6 administration is associated with attenuation of thrombin generation both in peripheral blood and at sites of hemostatic plug formation.
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PMID:Treatment of hyperhomocysteinemia with folic acid and vitamins B12 and B6 attenuates thrombin generation. 1052 5

Activation of the coagulation system in the alveolar space plays an important role in the pathogenesis of interstitial lung disease (ILD) and pulmonary fibrosis. The protein C (PC) pathway is the main modulator of coagulation activation. This study evaluated whether dysfunction of the PC pathway is associated with increased collagen synthesis in the intraalveolar space of patients with ILD. This study comprised 22 patients with ILD; of these, five had idiopathic pulmonary fibrosis (IPF), nine had sarcoidosis-associated ILD, and eight had collagen vascular disease-associated ILD (CVD-ILD). Thrombin-antithrombin complex (TAT) was measured as a marker of coagulation activation. As markers of the PC pathway activity, the concentration of activated PC-PC inhibitor (APC-PCI) complex and the APC-PCI/PC ratio were measured and, as a marker of collagen synthesis, the concentration of aminoterminal propeptide of type III procollagen (PIIINP) was measured in bronchoalveolar lavage fluid (BALF) of ILD patients. TAT was significantly increased in BALF from ILD patients as compared to control subjects. The concentrations of PIIINP were significantly elevated in patients with ILD as compared to healthy subjects. In contrast, the concentration of APC-PCI and the values of APC-PCI/PC ratio were significantly decreased in BALF from patients with ILD. BALF concentration of PIIINP was significantly and inversely correlated with the concentration of APC-PCI and with the APC-PCI/PC ratio. These findings suggest that dysfunction of the protein C pathway may have important physiopathologic implications in the development of pulmonary fibrosis in ILD.
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PMID:Decreased protein C activation is associated with abnormal collagen turnover in the intraalveolar space of patients with interstitial lung disease. 1103 May 25


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