Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The impact of long-term, heavy exercise on recently established cardiovascular/thromboembolic risk factors of the fibrinolytic system, tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in relation to food composition was studied. Twenty healthy men, aged 18-55 years participated in a 14-day skiing tour through the Swedish mountains, carrying a pack load of 30 kg, and spending each night in self-dug igloos (ambient temp -10 degrees to -25 degrees C), and were randomized to 2 food regimens having 30 or 40 energy percent of fat. Individual records were kept of all consumed food. Citrated plasma was obtained before and after 1 and 2 weeks of exercise: tPA release was assessed by a 10 min venous occlusion (VO) test. At baseline, daily dietary fiber intake correlated negatively with PAI-1 activity. Already after the first week of the skiing tour there were significant drops in PAI-1 activities, cholesterol and triglycerides. The tPA mass concentrations also dropped, both before and after VO, but tPA activities were unchanged, as were von Willebrand factor (vWF) levels. These changes were related mainly to the expenditure of energy, calculated from the food consumption, and appeared to be mediated through changed insulin sensitivity and decreased body fat mass. The energy percent of fat in the food had no differential impact. The effects receded a few weeks after cessation of the endurance exercise. Thus, endurance physical activity improves the fibrinolytic risk factor profile by reducing PAI-1 while leaving tPA activity unaffected, independently of food composition. A low dietary fiber intake appears to be associated with higher PAI-1 activities at baseline.
Atherosclerosis 1994 Mar
PMID:Endurance physical activity, diet and fibrinolysis. 801 8

The fibrinolytic capacity of blood depends mainly on the amount of tissue-type plasminogen activator (t-PA) activity and plasminogen activator inhibitor type-1 (PAI-1) activity. Previous studies linked high PAI activity or low t-PA activity with the development of atherosclerosis and thromboembolic diseases. Yet, there are conflicting reports in the literature as to whether there is higher PAI activity in patients with myocardial infarction (MI) than in patients with coronary artery disease (CAD) without previous MI. In this retrospective study, t-PA activity, t-PA antigen, and PAI activity before and after a venous occlusion test (VOT) of 10 min were assessed in 109 patients with angiographically documented CAD, in two subgroups of CAD patients with (n = 66) or without (n = 43) previous MI, and in subgroups of CAD patients according to their triglyceride levels and other risk factors. The mean values of t-PA activity in the whole patient group showed a 100-fold increase and a 3.1-fold increase in t-PA antigen after VOT (0.03 +/- 0.03 to 3.0 +/- 6.8 U/ml and 16.5 +/- 6.9 to 51.0 +/- 25.4 ng/ml, p < 0.05). PAI activity was 24.4 +/- 11.0 before and 19.6 +/- 13.2 U/ml after VOT. Within the CAD group, no difference was found between patients without MI and survivors of previous MI in PAI activity before VOT (24.6 +/- 10.7 vs. 24.3 +/- 11.3 U/ml) and after VOT (19.0 +/- 12.1 vs 20.0 +/- 14.0 U/ml), or t-PA activity before (0.03 +/- 0.01 vs. 0.04 +/- 0.04 U/ml) and after VOT (2.8 +/- 7.0 vs. 3.2 +/- 6.7 U/ml). In 39.4% of CAD patients elevated plasma PAI activity before VOT (> 25 U/ml) was found. This subgroup of patients represented the highest PAI activity after VOT (p < 0.05), the lowest t-PA activity after VOT (p < 0.001), and the highest triglyceride levels (p < 0.05). In 11% of the patients, a small increase in t-PA activity (less than 0.5 U/ml) after VOT was seen. This group showed the lowest t-PA antigen after VOT (p < 0.001) and the highest fibrinogen level (p < 0.05). Both subgroups showed the same distribution among patients with and without MI. CAD patients with triglyceride levels over 200 mg/dl had the highest PAI activity values before VOT (28.3 +/- 11.8 U/ml; p < 0.01) and after VOT (24.9 +/- 13.2 U/ml; p < 0.01), resulting in low t-PA activity after VOT (p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:High PAI activity with correlation to triglyceride and HDL cholesterol values in patients with coronary artery disease with no difference in survivors of myocardial infarction. 824 47

The aim of this study was to determine differences between cases of peripheral arterial disease and healthy controls in levels of haemostatic factors and lipid peroxides and the influence of cigarette smoking. The study groups were selected from the Edinburgh Artery Study which is a random sample survey of men and women aged 55-74 years. Mean levels of plasma fibrinogen, von Willebrand factor, beta-thromboglobulin, plasminogen activator inhibitor (type I), cross-linked fibrin degradation products and lipid peroxides were markedly elevated in 121 study cases compared with 126 age- and sex-matched controls. For example, cross-linked fibrin degradation products had a geometric mean of 106.8 ng/ml (95% confidence interval (CI) 95.3, 119.8) in study cases and 74.7 ng/ml (95% CI 67.0, 83.4) in controls (P < 0.001). Inclusion of smoking in logistic regressions of each factor on peripheral arterial disease significantly reduced the odds of disease for von Willebrand factor and for cross-linked fibrin degradation products, but had little effect on the increased odds associated with fibrinogen, beta-thromboglobulin, plasminogen activator inhibitor and lipid peroxides. We conclude that, in men and women in Edinburgh, peripheral atherosclerosis is associated with lipid peroxidation, endothelial disturbance, platelet activation, elevated fibrinogen, fibrin formation and increased inhibition of fibrinolysis. The most important effects of cigarette smoking in promoting atherosclerosis may be endothelial disturbance and fibrin formation.
Atherosclerosis 1993 Sep
PMID:Smoking, haemostatic factors and lipid peroxides in a population case control study of peripheral arterial disease. 825 Oct 1

Accelerated atherosclerosis is the leading cause of death in patients with non-insulin-dependent diabetes mellitus (NIDDM). Impaired endogenous fibrinolytic activity may accelerate atherosclerosis by exposing vascular luminal wall surfaces to persistent and recurrent thrombi and clot-associated mitogens. This study was conducted to further characterize endogenous fibrinolysis in lean and obese nondiabetic subjects and in NIDDM patients and to identify mechanisms responsible for the alterations identified. Obese and diabetic subjects had threefold elevations of plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1) compared with values in lean control subjects. Despite the lack of significant differences in plasma concentrations of tissue-type plasminogen activator in the obese and diabetic subjects, both basal and stimulated endogenous fibrinolytic activities were decreased. The decreases were associated with increased activity of PAI-1 in plasma, in turn correlated with increased concentrations of immunoreactive insulin and C-peptide. These results are consistent with our previous observations demonstrating direct stimulatory effects of insulin and its precursors on cellular expression of PAI-1 in vitro and observations by others demonstrating decreased basal fibrinolytic activity in NIDDM patients. Impaired endogenous fibrinolytic activity could lead to prolonged or recurrent exposure of luminal surfaces of vessel walls to microthrombi and clot-associated mitogens that may accelerate atherosclerosis in hyperinsulinemic subjects.
 ...
PMID:Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients. 826 7

The effect of different fat loads on postprandial lipemia and hemostatic activity was examined in 10 middle-aged men using 3 different meals. One meal was rich in saturated fatty acids (cream), the other rich in n-6 polyunsaturated fatty acids (sunflower oil) and the third was fat-free containing only carbohydrates. Lipoprotein lipids and hemostatic parameters were measured during fasting and 2, 4, 6 and 8 h after the test meal. In fasting samples, several hemostatic parameters were significantly associated with lipoprotein lipids. Most notable were the strong associations of fibrinolysis parameters tissue plasminogen activator antigen and plasminogen activator inhibitor activity (PAI-1) with total and very low density lipoprotein (VLDL) triglycerides. During lipemia, the associations were approximately similar or slightly weaker than in the fasting state. Both fat loads resulted in similar postprandial lipid responses: VLDL and high density lipoprotein (HDL) triglycerides reached maximum at 4 h after the meal. VLDL cholesterol also increased 4 and 6 h after the fat loads. HDL3 cholesterol declined after the fatty meals but no change was observed in the HDL2 fraction. The fat-free meal gave no significant lipid changes during the time course studied. Factor VII activity (F VII:C) increased 6 and 8 h after the fatty meals, whereas a decrease was observed after the fat-free meal. The changes (+/- S.D.) at 8 h after cream, sunflower oil and fat-free meal were 5.2 +/- 3.3, 3.3 +/- 4.2 and -5.8 +/- 7.9 percentage points, respectively, and the effect of the meal on the changes was statistically significant (F (8,99) = 2.99, P = 0.0048). F VII antigen (F VII:Ag) tended to decline during the day but there was no difference between the meals. Factor VIII activity (F VIII:C) was highest after the polyunsaturated fat meal and lowest after the fat-free meal. PAI-1 declined during the day and the decline tended to be steepest after the fat-free morning meal. The effect of the meal on the changes in lipoprotein lipids and hemostatic factors varied significantly between individuals. In conclusion, postprandial lipemia after a single fatty meal was associated with procoagulatory change in F VII:C but there was no difference between saturated fat and n-6 polyunsaturated fat.
Atherosclerosis 1993 Oct
PMID:The effects of saturated fat and n-6 polyunsaturated fat on postprandial lipemia and hemostatic activity. 828 Jan 80

The capacity of macrophages to influence directly and indirectly fibrinolytic processes in atherosclerosis was studied using macrophages isolated from atherosclerotic plaques of patients undergoing surgical repair of distal aortic and femoral arteries. These cells were characterized by their morphology, adherence, esterase positivity, and expression of CD14 antigen. Production of plasminogen activator inhibitor type-1 (PAI-1) by plaque macrophages (6.7 +/- 2.7 ng/10(5) cells/24 hours [mean +/- SEM]) was significantly greater than PAI-1 production by blood monocytes isolated simultaneously from the same patients (1.8 +/- 1.5 ng/10(5) cells/24 hours). Production of tissue type plasminogen activator and urokinase type was not augmented compared to blood monocytes. Conditioned medium from cultured plaque macrophages significantly increased production of PAI-1 by endothelial cells (85 +/- 11% above basal) and vascular smooth muscle cells (25 +/- 10%) in vitro. This response was significantly greater than the response to monocyte-conditioned medium (endothelial cells 38 +/- 11%, vascular smooth muscle cells 2.5 +/- 2.0%). Stimulation of endothelial cell PAI-1 production by macrophage-conditioned medium was partially inhibitable by a monoclonal antibody to transforming growth factor-beta. Tissue type plasminogen activator production by endothelial cells and vascular smooth muscle cells was not affected by plaque macrophage- or monocyte-conditioned medium. Urokinase type plasminogen activator production by endothelial cells and vascular smooth muscle cells was undetectable in control medium and was augmented to similar levels in response to plaque macrophage- and monocyte-conditioned media. These results demonstrate upregulation of PAI-1 production by macrophages in atheromatous plaques and the capacity of soluble products from plaque macrophages to upregulate PAI-1 production by endothelial cells and vascular smooth muscle cells in vitro. These data suggest that macrophages in atherosclerotic plaques may inhibit thrombolysis both directly and indirectly by effects of their soluble products on endothelial cells and vascular smooth muscle cells.
 ...
PMID:Atheromatous plaque macrophages produce plasminogen activator inhibitor type-1 and stimulate its production by endothelial cells and vascular smooth muscle cells. 836 83

Tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor antigen (PAI-1), soluble P-selectin and von Willebrand factor antigen (vWf) were measured by ELISA in 41 patients with peripheral vascular disease (PVD), 41 with ischaemic heart disease (HD) and in 46 age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0002) and in patients with PVD (p = 0.0011) relative to the controls but levels did not differ between the two patients groups. Raised tPA found in both PVD (p = 0.0006) and IHD (p = 0.0061) compared to the controls also failed to differentiate the two groups of patients. Soluble P-selectin was also raised in both groups (p = 0.003 in IHD and p = 0.0102 in PVD) with no difference between the groups. There were no differences in levels of PAI-1 between the groups. In the subjects taken as a whole, there were significant Spearman's correlations between tPA and vWf (r = 0.37, p < 0.001), tPA and triglycerides (r = 0.38, p < 0.001), tPA and P-selectin (r = 0.19, p = 0.032), vWf and age (r = 0.25, p = 0.005) and inversely between vWf and HDL (r = -0.25, p = 0.006). These data support the concept that increased levels of tPA may be important in atherosclerosis, and indicate that soluble P-selectin may be useful in further analysis of the role of platelets and the endothelial cell in this disease.
 ...
PMID:von Willebrand factor, soluble P-selectin, tissue plasminogen activator and plasminogen activator inhibitor in atherosclerosis. 858 97

Three enzyme-linked immunosorbent assays for the quantitation of murine tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor 1 (PAI-1), were developed using monoclonal antibodies raised against the autologous proteins in gene-inactivated mice. Dose-response was linear for t-PA and PAI-1 between 5 and 0.1 ng/ml and for u-PA between 50 and 1 ng/ml, with intra-assay, inter-assay and inter-dilution coefficients of variation of 6 to 14%. Assay recoveries of proteins (5 to 100 ng/ml) added to plasma were 73 to 95% for t-PA and PAI-1. Linear correlations (r = 0.65, r = 0.91 and r = 0.92, for t-PA, u-PA and PAI-1 respectively) were found between antigen and activity in plasma, urine and tissue extracts. Levels of t-PA and PAI-1 antigen in murine plasma were 2.5 +/- 1.0 ng/ml (mean +/- SD, n=9) and 1.9 +/- 0.6 ng/ml (mean +/- SD, n = 8), respectively, in wild-type mice and undetectable in gene-inactivated mice. Bradykinin injection in mice provoked a 12-fold increase (p < 0.0002) of t-PA and endotoxin injection an 80-fold increase (p < 0.005) of PAI-1 levels. u-PA antigen levels in urine from wild-type mice ranged between 0.2 and 8.2 micrograms/ml (1.8 +/- 1.9 micrograms/ml, mean +/- SD, n = 17) and were undetectable in gene-inactivated mice. Thus, these assays may be useful for studies on the role of these proteins in tissue remodeling, atherosclerosis, embryogenesis, etc., in established mouse models. Gene-inactivated mice may constitute a general approach for the generation of monoclonal antibodies against the deficient translation products and for the development of specific immunoassays for murine proteins.
 ...
PMID:Immunoassay of murine t-PA, u-PA and PAI-1 using monoclonal antibodies raised in gene-inactivated mice. 860 14

Atherosclerosis and thrombosis, two major causes of morbidity and mortality in renal transplant recipients, share the same clinical risk factors including decreased fibrinolysis and lipid disturbances. In a cross-sectional study we have determined parameters of fibrinolysis in control subjects (n = 23) and stable renal allograft recipients without cyclosporin (CsA) (n = 10) and with CsA (n = 87) in their immunosuppressive treatment. In CsA-treated patients, tissue-type plasminogen activator was moderately increased compared to patients without CsA (8.4+/-3.3 vs 5.5+/-2.8 ng/ml). The plasminogen activator inhibitor (PAI) activity in plasma was clearly increased in CsA-treated patients: 14.5+/-8.8 vs 7.2+/-3.2 in normal controls and 8.5+/-2.4 AU/ml in patients without CsA. Total cholesterol and LDL cholesterol levels were higher in CsA-treated patients (256+/-62 and 169+/-60 mg/dl) than in patients without CsA (209+/-45 and 136+/-44 mg/dl). The two groups did not differ in HDL cholesterol, triglycerides, and lipoprotein(a). Hypercholesterolaemia, obesity, and steroid-induced diabetes could be identified as risk factors for elevated plasma PAI activity in CsA-treated patients. Hypofibrinolysis induced by elevated PAI levels and increased LDL cholesterol may contribute to the increased thrombogenicity and accelerated atherosclerosis observed in cyclosporin-treated patients.
 ...
PMID:Elevated plasminogen activator inhibitor levels in cyclosporin-treated renal allograft recipients. 867 91

The aim of this study was to examine whether there was a relationship between ultrasound-assessed morphology of the femoral artery wall and hemostatic factors, and whether these factors were associated with intermittent claudication. One hundred and thirty men at high cardiovascular risk and 51 men at low risk were examined. The subjects (high- and low-risk) with moderate/large plaque (n = 96) had higher fibrinogen, thrombin/antithrombin complex and von Willebrand factor, compared to subjects with small/no plaque. The maximum intima-media thickness of the femoral artery was significantly associated with fibrinogen. These associations were independent of current smoking habits. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex, plasminogen activator inhibitor activity, mean and maximum intima-media thickness and plaque status of the femoral artery. In conclusion, fibrinogen, von Willebrand factor and thrombin/antithrombin complex were related to plaque occurrence in the femoral artery. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex and plasminogen activator inhibitor activity.
 ...
PMID:Femoral artery wall morphology, hemostatic factors and intermittent claudication: ultrasound study in men at high and low risk for atherosclerotic disease. 869 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>