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

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria. 162 64

The plasma levels of several haemostatic and fibrinolytic parameters were measured before and after delivery in 61 hypertensive pregnant women of whom 22 developed preeclampsia, and compared to the results obtained in 42 normal pregnant women. In the two last weeks before delivery (D less than or equal to -15) tPA antigen, PAI-1 activity, vWF:Ag/FVIII:C ratio, ATIII activity and platelet count were found to be significantly different in the hypertensive pregnant women with and without preeclampsia. Combined all together, an association of three of these five parameters were found to be pathological (i.e.:tPA:Ag greater than or equal to 19 ng/ml, PAI-1 activity greater than or equal to 58 IU/ml, vWF:Ag/FVIII:C ratio greater than or equal to 2.6, ATIII activity less than or equal to 73%) in none of the hypertensive women without preeclampsia and in only 35% of the preeclamptic group. A positive correlation was demonstrated between vWF:Ag/FVIII:C ratio and tPA:antigen levels suggesting that both tPA and vWF:Ag could be considered as early indicators of a possible micro angiopathy occurring in preeclampsia. However, due to the high dispersion of the results, it appears that the investigated haemostatic and/or fibrinolytic criteria give only presumptive arguments before assigning risk for preeclampsia development among hypertensive pregnant women.
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PMID:Are haemostatic and fibrinolytic parameters predictors of preeclampsia in pregnancy-associated hypertension? 179 89

Type II (non-insulin dependent) diabetes is associated with a high incidence of vascular disease that causes morbidity and mortality. The principal organs affected by this process are the heart, brain and lower limbs. For many years it has been proposed that depression of the fibrinolytic system, which acts to maintain patency of blood vessels, may contribute to the development of vascular disease. A number of pharmacological agents have been shown to enhance circulating fibrinolytic activity of which metformin is perhaps the most interesting because of its low incidence of serious side effects. Early studies with metformin demonstrated an increase in global fibrinolytic activity in patients with coronary artery disease, peripheral vascular disease and diabetes. Recent studies using assays specific for the components of the fibrinolytic system have shown that the effects of metformin are to cause a fall in plasma levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1). There is evidence to suggest that the relationship between depressed fibrinolysis and vascular disease is due to high levels of PAI-1, and reasons to believe that a lowering of PAI-1 may be beneficial in this respect. Further studies are warranted to evaluate the long term effects of metformin warranted to evaluate the long term effects of metformin on the incidence of vascular disease in diabetic patients.
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PMID:The effects of metformin on the fibrinolytic system in diabetic and non-diabetic subjects. 193 71

Diabetes mellitus (DM) is associated with an increased incidence of vascular complications. Abnormalities in the hemostatic system contribute at least in part to the development of vascular disease or atherosclerosis. In order to assess the actual degree of activation of the coagulation and fibrinolytic systems in diabetics, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP) were measured together with tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 18 patients with DM (three patients with type I DM and 15 with type II DM). Mean plasma levels of TAT (2.5 +/- SD 1.2 ng/mL) and PAP (0.9 +/- 1.2 micrograms/mL) were significantly elevated in diabetics as compared with healthy subjects (1.7 +/- 0.3 ng TAT and 0.2 +/- 0.1 micrograms PAP per mL of plasma; p = 0.009 and 0.02, respectively). Plasma antigen concentration of t-PA but not of PAI-1 was also elevated. No difference was found in the levels of these variables between type I and type II diabetics or between patients with and without retinopathy or nephropathy. These findings indicate that continuous activation of coagulation and fibrinolysis actually occurs in the majority of the patients with DM.
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PMID:Activation of blood coagulation and fibrinolysis in diabetes mellitus: evaluation by plasma levels of thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex. 238 33

In summary, studies of the expression of fibrinolytic genes in the vessel wall suggest an active, ongoing proteolytic process, the activity of which is dependent on the relative amounts of tPA, uPA, and PAI-1 secreted and locally deposited. Disturbances in the balance of pro- and antifibrinolytic activity in atherosclerotic vessels have considerable potential for influencing both intra- and extravascular fibrinolytic events and may be causally related to the development of vascular disease.
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PMID:Abnormalities in the fibrinolytic system of the vascular wall associated with atherosclerosis. 753 27

The authors investigated the behaviour of some markers of the haemostatic balance in a group of patients with acute focal cerebral vasculopathy. The series consists of 70 female patients (mean age: 61 +/- 5), 25 of whom suffering from TIA and 45 from thrombotic stroke; 40 normal controls (mean age 43 +/- 5) were also considered. For each patient after an overnight fasting a withdrawal of venous blood was done within 24-36 hours after the admission. For each sample the determination of seven prothrombotic markers [(fibrinogen (F), factor VII (F VII), antithrombin III (AT III), protein C (PC), protein S (PS) (coagulometric method IL), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) (ELISA method Boehringer)] and of three prethrombotic markers [(fibrinopeptide A (FPA), beta-thromboglobulin (BTG) and D-dimer (D-D) (ELISA method, Boehringer)] was performed. The results obtained in the group of the cerebrovasculopathic patients compared to the controls showed a significant increase of F (p < 0.001), F VII (p < 0.005), BTG (p < 0.05) and D-D (p < 0.01), whereas significant differences regarding AT III, PC, PS, t-PA, PAI and FPA were not observed. The authors hypothesized that the increased levels of fibrinogen and factor VII in the cerebrovascular subjects, globally considered, may depend on a marked prothrombotic state, linked in a pathogenetic sense to the vascular disease; the existence of a prethrombotic state is also documented by the increase of betathromboglobulin and D-dimer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Haemostatic balance in patients with acute focal cerebral vasculopathy. 760 35

Hypopituitary patients on routine replacement therapy except growth hormone (GH) have an increased risk of death from cardiovascular diseases compared with healthy subjects. Untreated GH deficiency might explain the premature death from vascular disease. Plasminogen activator inhibitor (PAI-1) activity, fibrinogen, insulin, blood lipid, and blood pressure levels were studied in 20 GH-deficient adults (10 men, 10 women) 50 +/- 11 years old with routine hormone replacement therapy (except GH) and compared with 20 healthy control subjects matched for sex, age, and body mass index. GH-deficient subjects had a higher waist-to-hip circumference ratio (P < .001), serum triglycerides (P < .02), PAI-1 activity (13.2 +/- 10.6 versus 6.8 +/- 4.8 U/mL [P < .05]), and fibrinogen (3.2 +/- 0.7 versus 2.4 +/- 0.6 g/L [P < .001]) and lower blood glucose (P < .05) compared with control subjects. Blood pressure, insulin, and cholesterol levels were similar. The aberrations found in this study might contribute to an increased atherothrombotic propensity and play a role in the pathogenesis of cardiovascular disease.
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PMID:High fibrinogen and plasminogen activator inhibitor activity in growth hormone-deficient adults. 812 48

Blackfoot disease is a unique endemic and chronic progressive arteriosclerotic vascular disease in southwest area of Taiwan. In this study, we determined the plasma levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), urokinase plasminogen activator (uPA), and von Willebrand factor (vWF) antigen in Blackfoot disease patients, in comparison with normal controls from non-endemic areas and the endemic area, Putai. Blackfoot disease patients had mean tPA antigen level of 7.9 ng/ml (n = 27) which was significantly lower (p < 0.05) than both the normal controls with 11.0 ng/ml (n = 20) and the Putai normal controls with 9.7 ng/ml (n = 39). However, the mean PAI-1 antigen level in the patient group was 41.2 ng/ml (n = 28) which was significantly higher (p = 0.0001) than both the normal controls with 19.7 ng/ml (n = 23) and the Putai normal controls with 21.3 ng/ml (n = 40). Furthermore, in the patient group, a significantly lower (p < 0.005) mean uPA antigen level (2.3 ng/ml, n = 18) was noted as compared with that in the normal controls (3.2 ng/ml, n = 14). No significant difference was observed in vWF antigen level between patients and normal controls. This study suggests that a reduced capacity for fibrinolysis is associated with Blackfoot disease.
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PMID:Impaired fibrinolysis in patients with Blackfoot disease. 830 60

It is not clear whether elevated levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAl-1) in Type 2 diabetes mellitus are the result of obesity or coexistent atherosclerosis. Therefore the relationship between PAl-1 and insulin resistance, determined by the homeostasis model assessment (HOMA) was investigated in a group of 26 insulin-resistant, normotensive newly diagnosed Type 2 diabetic patients with a low probability of atherosclerosis. Compared with a normal control group, closely matched for body mass index (BMI), fibrinolytic activity was depressed in the diabetic patients due to elevated levels of the inhibitor PAl-1, 17.6 (11.1-28) vs 8.4 (4.9-14.1) IU ml-1, p < 0.001. PAl-1 was related to BMI, r = 0.59, p < 0.001 plasma insulin, r = 0.66, p < 0.001; insulin resistance, r = 0.54, p < 0.005 and urinary albumin excretion, r = 0.48, p < 0.01, but not HbA1c or fasting glucose. PAl-1 was not related to blood pressure or plasma triglyceride levels. This study suggests that at the time of diagnosis of Type 2 diabetes mellitus, elevated PAl-1 levels are already linked to other risk factors for vascular disease including hyperinsulinaemia, insulin resistance, and urinary albumin excretion, and this is not the result of obesity or coexistent atherosclerosis.
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PMID:The relationship between plasminogen activator inhibitor-1 and insulin resistance in newly diagnosed type 2 diabetes mellitus. 840 25

Local accumulation of plasminogen activator inhibitor-1 (PAI-1) in response to thrombosis has been implicated not only in inhibition of fibrinolysis but also in the pathogenesis of vascular disease. To determine whether thrombin, known to be released from thrombi, can induce expression of PAI-1 in vascular smooth muscle, bovine aortic smooth muscle cells were exposed to highly purified bovine thrombin. Thrombin, in the absence of serum, induced production of PAI-1 by bovine aortic smooth muscle cells in a dose-dependent manner. PAI-1 activity in the conditioned media reached a maximum with 12 nM thrombin. Metabolic labeling with [35S]methionine demonstrated that the elaborated PAI-1 was newly synthesized and that it comprised both a cleaved inactive 42-kd form and an uncleaved active 46-kd form. The increase of PAI-1 activity in the media paralleled the thrombin-induced increase in the concentration of the 46-kd form. Preincubation of thrombin with hirudin, a specific inhibitor of thrombin, or with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, an inhibitor of the active site of thrombin, prevented the induction of PAI-1 synthesis. The stimulatory effect of thrombin on PAI-1 synthesis was also evident at the level of expression of mRNA, with steady-state PAI-1 mRNA levels increasing by 100% in 4-8 hours. When the bovine aortic smooth muscle cells were exposed to transforming growth factor-beta 1, an agonist shown previously to increase PAI-1 synthesis in diverse cell types, synergy with thrombin was evident.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of vascular smooth muscle cell expression of plasminogen activator inhibitor-1 by thrombin. 841 45


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