Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein(a) (Lp(a)) has been established as an important independent risk factor for the development of cardiovascular disease. Apolipoprotein(a), together with apo B-100 the apolipoprotein of Lp(a), is homologeous to plasminogen but lacks fibrinolytic capacity and appeared to interfere with fibrinolysis in in vitro and ex vivo experiments. We determined the correlations between Lp(a) and other blood lipids (serum cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), coagulation parameters (fibrinogen, factor VII, factor VIII:C fibrin monomers, thrombin-antithrombin III) and fibrinolysis parameters (tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and D-dimer) in 54 patients with essential hypertension, in 65 non-insulin-dependent diabetic patients and in 116 insulin-regulated diabetic patients. Signs of activated coagulation and increased reactive fibrinolysis were found in all three patient groups. In the hypertensive patients, Lp(a) was significantly correlated with LDL-cholesterol (r = 0.25, P = 0.04) and triglycerides (r = -0.30, P = 0.03), while in insulin-regulated diabetics, Lp(a) was also correlated with LDL-cholesterol (r = 0.20, P = 0.03). In the hypertensive patients and both diabetic groups there was no correlation of Lp(a) with coagulation or fibrinolysis parameters. These data show that Lp(a) concentrations are not related to coagulation or fibrinolysis parameters in hypertensive or diabetic patients and confirm the presence of an activated coagulation system in these patient groups.
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PMID:Low order correlations of lipoprotein(a) with other blood lipids and with coagulation and fibrinolysis parameters in hypertensive and diabetic patients. 138 33

The correlations between the cardiovascular risk factors hypertension, overweight, hyperlipidemia and fibrinolysis parameters were studied in a group of 54 otherwise healthy patients (age 19 to 70 years) with essential hypertension of moderate severity. Of the 54 patients 43 were treated with antihypertensive drugs and eleven were not. The patients included in this study who were treated with antihypertensive drugs were, in spite of their treatment, still hypertensive. Lipoprotein levels and fibrinolysis parameters did not differ between the untreated and treated patients. In the patient group we found significant incidence of hypertriglyceridemia (46%) elevated LDL-cholesterol (28%) and elevated lipoprotein (a) levels (43%). In comparison with a healthy control group the hypertensive patient group showed a decreased median tissue plasminogen activator activity (interquartile range): 0.23 (0.79) IU.10(3)/l vs 1.5 (0.47) IU.10(3)/l in the controls (p less than 0.0001), an increased tissue plasminogen activator antigen concentration: 8.2 (4.5) micrograms/l vs 5.1 (3.9) micrograms/l in the controls (p less than 0.0001), an elevated plasminogen activator inhibitor-1 level: 2.8 (2.5) AU.10(3)/l vs 1.1 (2.0) AU.10(3)/l in the controls (p less than 0.01) and a slightly increased alpha 2-antiplasmin concentration: 110 (8)% vs 98 (16)% in the controls (p less than 0.0001). Median D-dimer concentration levels were substantially increased in the hypertensive patients: 315 (263) micrograms/l vs 199 (146) micrograms/l in the controls (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrinolysis factors and lipid composition of the blood in treated and untreated hypertensive patients. 162 20

Platelet function was investigated in healthy volunteers and patients with essential hypertension by measurement of thresholds for ADP and adrenaline-induced aggregation and plasma concentrations of platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG) after administration of antihypertensive drugs. Fibrinolytic activity was investigated by the euglobulin clot lysis time (ECLT) and tissue plasminogen activator (t-PA) activity. Compared to normotensive controls, patients with essential hypertension showed increased aggregation as evidenced by a decrease in ADP thresholds for ex vivo platelet aggregation. ECLT was significantly prolonged and t-PA significantly lowered, indicating impaired fibrinolytic activity in mild hypertension. In different studies, we have shown that various antihypertensive drug regimens differ in their effects on platelet function and fibrinolytic activity when given to healthy volunteers or patients with mild-to-moderate essential hypertension. In normal volunteers, treatment with the calcium antagonists verapamil, nifedipine, and felodipine lowered plasma concentrations of PF-4 and beta-TG, indicating a reduced platelet activity in vivo. Fibrinolytic activity was not influenced by calcium antagonist treatment in the normal volunteers. Interestingly, however, t-PA increased significantly in the hypertensive group. When compared to placebo or beta 1-selective blockers, propranolol, a non-selective beta-adrenergic blocker without partial agonist activity, reduced ADP and adrenaline threshold values for ex vivo platelet aggregation in hypertensive subjects and impaired fibrinolytic activity in the normal volunteers as well as in the hypertensive groups by increasing ECLT and reducing t-PA. Hypothetically, the effects of antihypertensive drugs on platelet function and fibrinolytic activity could be of importance for their proposed actions on cardiovascular morbidity and mortality.
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PMID:Platelet function and fibrinolytic activity in hypertension: differential effects of calcium antagonists and beta-adrenergic receptor blockers. 172 42

The aim of this study was to assess the function of the fibrinolytic system at rest and in response to adrenergic stimulation in patients with stable essential hypertension as compared with normotensives. At rest, essential arterial hypertensives were characterized by increased levels of circulating tissue-plasminogen activator, associated with an increased activity of its specific inhibitor, the PAI-1. After stress, fibrinolytic response was impaired in essential arterial hypertensives despite a greater release of tissue plasminogen activator by endothelial cells. Therefore, the PAI-1 activity may be increased in essential arterial hypertensives not only at rest, but also after stress. This may represent a risk factor for hypertensive patients.
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PMID:Decreased fibrinolytic response to adrenergic stimulation in hypertensive patients. 251 1

The aim of this study was to assess the cardiovascular and hormonal responses to 1-desamino-8,D-arginine vasopressin (DDAVP) in hypertensive patients before and after non-selective beta-blockade. We infused DDAVP at 400 ng/kg body weight for 10 min in nine subjects with mild essential hypertension before and 14 days after administration of nadolol at 80 mg/day. Blood pressure and heart rate were recorded, and blood was drawn at 0, 30 and 60 min for measurement of plasma renin activity, aldosterone, cortisol, noradrenaline, adrenaline and dopamine. Before the administration of nadolol, DDAVP induced a significant decrease in blood pressure, and significant increases in the heart rate, plasma renin activity, cortisol and noradrenaline; there were no changes in adrenaline or dopamine. After the administration of nadolol, baseline noradrenaline was significantly increased, while cortisol, adrenaline and dopamine remained unchanged. A second infusion of DDAVP did not significantly alter blood pressure, [corrected] heart rate, noradrenaline, adrenaline or dopamine, but plasma renin activity, aldosterone and cortisol still showed a significant increase. The blunted hypotensive effect of DDAVP after the administration of nadolol may be aspecific, due to lower basal blood pressure levels, or may indicate a mechanism of action common to both drugs. A similar post-DDAVP increase before and after beta-blockade suggests that the drug has a direct effect on the renin-secretory apparatus. An indirect effect, mediated by changes in intrarenal haemodynamics or by other factors with renin-stimulating activity, e.g. tissue plasminogen activator, can also be hypothesized.
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PMID:Cardiovascular and hormonal responses to DDAVP before and after beta-blockade in patients with mild essential hypertension. 307 98

In 22 untreated patients with uncomplicated essential hypertension and in 10 normotensive subjects the plasma levels of thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor (PAI-1) were evaluated. The observed values show no significant difference in plasma TM, plasma and urine beta-TG concentration and plasma DD among hypertensive patients and controls. On the other hand, the levels of t-PA and PAI-1 in hypertensive patients were significantly higher than the values detected in normotensive control subjects. These data seem to indicate that, at initial stages of essential hypertension, the t-PA and PAI-1 levels increase.
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PMID:Haemostatic variables in arterial hypertension. 748 62

Despite effective antihypertensive therapy, essential hypertension is still associated with considerable residual risk of cardiovascular complications. The aim of the present study was to investigate the state of the endogenous fibrinolytic system in young subjects with borderline hypertension. Thirty-nine young (age, 24 to 34 years) male subjects with borderline hypertension (systolic BP [SBP] 140 to 160 mm Hg and/or diastolic BP [DBP] 85 to 95 mm Hg) and 17 normotensive control subjects (age, 22 to 31 years; SBP 110 to 130 and DBP 60 to 80 mm Hg) were recruited from a population screening. Plasma levels of tissue-type plasminogen activator (t-PA) antigen and activity and plasminogen activator inhibitor 1 (PAI-1) antigen were determined at rest and in response to a venous occlusion test. Borderline-hypertensive subjects had metabolic and anthropometric characteristics similar to normotensive individuals. In comparison with normotensive subjects, borderline-hypertensive subjects had higher plasma concentration of t-PA antigen both at rest and after venous occlusion but similar levels of t-PA activity or PAI-1 antigen. The increase in t-PA antigen and activity in response to venous occlusion was significantly greater in borderline-hypertensive subjects than in normotensive control subjects (P < .0001 and P = .003, respectively). In stepwise regression analyses, 24-hour mean arterial pressure emerged as the single most powerful predictor of t-PA antigen levels, but body mass index was the most important determinant of t-PA activity and PAI-1 antigen. However, PAI-1 was explained by both body mass index (partial r = .48, P < .001) and 24-hour mean arterial pressure (partial r = .29, P < .05). Thus, early hypertension may be associated with significant alterations in endogenous fibrinolysis.
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PMID:Enhanced levels of tissue-type plasminogen activator in borderline hypertension. 759 Oct 20

The incidence of atherosclerotic and thromboembolic complications is quite high in hypertensive patients. Blood platelets and fibrinolytic activity may play an important role in the development of these complications. We investigated fibrinolytic activity and in vivo platelet release reaction in essential hypertension. Plasma levels of beta thromboglobulin (BTG), platelet factor-4 (PF4), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and plasminogen were determined in 36 essential hypertensive and 20 age and sex-matched control subjects. Plasma BTG levels were significantly higher in the hypertensive subjects than in controls (p < 0.05), whereas PF4 levels were similar for both groups suggesting an increase of in vivo platelet activity. PAI-1 antigen levels were found to be significantly higher in the hypertensive patients as compared to the control subjects (p < 0.01). On the other hand significant variations of t-PA antigen and plasminogen values were not observed in the two groups. These results suggest that essential hypertension is associated with decreased fibrinolytic activity and enhanced platelet activity as evidenced by high plasma levels of PAI-1 and BTG.
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PMID:Fibrinolytic activity and platelet release reaction in essential hypertension. 789 22

This study assessed the effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on the main haemostatic variables in 22 patients, of either sex, with newly diagnosed uncomplicated essential hypertension. In the patients and in 10 control subjects, plasma levels of thrombomodulin, beta-thromboglobulin, D-dimer, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) had previously been measured. Only the levels of t-PA and PAI-1 were found to be higher than in controls. All these haemostatic evaluations were carried out after 6 and 12 months of treatment with an ACE inhibitor, cilazapril, 5 mg/day. This treatment significantly lowered the mean arterial pressure in the whole group from 133 to 106 mm Hg (after 6 months) and to 105 mm Hg (after 12 months), p < 0.05. No significant difference in any haemostatic parameters was observed after 6 and 12 months of treatment. The present study confirmed that treatment with cilazapril for 12 months lowers daytime ambulatory mean arterial pressure in patients with essential hypertension, without any significant increase in the tendency of blood to clot.
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PMID:Effects of medium-term antihypertensive therapy on haemostatic parameters in patients with essential hypertension. 909 84

Among cardiovascular diseases, hypertension, angina pectoris, acute myocardial infarction and ischemic stroke present a circadian pattern with a greater incidence of unfavourable events between awakening and noon. Chronotherapy aims to use drugs that release their active principles at different times during the day, according to biological needs. In chronotherapy of cardiovascular diseases, a particular attention has been paid to slow-release drugs that assure a 24 hours therapeutic effect with once a day administration. In primary hypertension well controlled by monotherapy (dipper hypertensives), the morning administration of long-acting beta-blockers and calcium antagonists has shown to control blood pressure over 24 hours, whereas ACE-inhibitors have proved more effective when administered at evening. In secondary hypertension (non dipper hypertensives) the administration of calcium antagonists is more effective at evening. Patients with severe hypertension need polytherapy. In that case, at least one of the antihypertensive drugs should be given at evening to lower night blood pressure values, which are particularly elevated also during sleep, and so to prevent an excessive blood pressure rise on awakening. In chronic monotherapy of ischemic heart disease, long-acting beta-blockers and calcium antagonists have shown to be equally effective when they are administered at morning, whereas slow-release nitrates, which need a nitrate-free interval, are to be administered either at morning or at evening, according to the expected time of onset of anginal pain. ASA seems to reduce the morning incidence of acute myocardial infarction, while tissue-type plasminogen activator presents a circadian variation of its thrombolytic activity with a higher efficacy between noon and midnight.
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PMID:[Application of chronotherapy to cardiovascular diseases]. 979 79


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