Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen Japanese patients of both sexes aged 46-78 years with essential hypertension were studied at the cardiac clinic of the Department of Cardiology, Shizuoka General Hospital, Shizuoka, Japan. Serum lipids, lipoproteins, plasma fibrinolytic parameters, renin and noradrenaline were determined before and after 3 months of cilnidipine treatment. Systolic and diastolic blood pressures and heart rate were reduced while renin and noradrenaline levels remained unchanged after cilnidipine treatment. Total cholesterol and tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and t-PA-PAI-1 complex were reduced. Changes in the other lipids, lipoproteins and fibrinolytic parameters were not significant after cilnidipine treatment. A negative correlation was found between low-density lipoprotein cholesterol and t-PA antigen levels after cilnidipine treatment. In conclusion, cilnidipine was effective for the treatment of hypertension and did not cause reflex tachycardia in Japanese patients. Cilnidipine treatment produced a beneficial lipid profile (decrease in total cholesterol), but did not show a consistent effect on fibrinolytic parameters in hypertensive patients. The metabolic interaction between beneficial lipid changes and fibrinolysis will be of value to better our understanding of the antiatherogenic effects of cilnidipine treatment in hypertensive patients.
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PMID:Effects of cilnidipine on lipids, lipoproteins and fibrinolytic system in hypertensive patients. 1110 11

Accumulating data support an association between hypertension and impaired fibrinolytic potential abnormalities in endogenous fibrinolysis. The present study examined whether there was an association between essential hypertension and either a polymorphism in the gene coding for t-PA or the plasma concentration of t-PA antigen. Chinese hypertensive subjects (n = 126) and normotensive controls (n = 102; sex- and age-matched with hypertensives) were recruited from among the outpatients of FuWai Hospital. The distributions of the II, ID, and DD genotypes of the t-PA gene in hypertensive patients (0.15, 0.49, 0.36) were similar to those in control subjects (0.11, 0.51, 0.38; p = 0.626). No significant difference in overall allele frequencies was found between the hypertension and control groups (p = 0.656). The allelic frequencies were in Hardy-Weinberg equilibrium. There was no evidence of an association between the level of t-PA antigen and risk of hypertension. Thus, in this case control study, neither the presence of the insertion allele of the Alu-repeat polymorphism of the t-PA nor the level of t-PA antigen were associated with the risk of essential hypertension.
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PMID:Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator and the risk of hypertension in a Chinese Han population. 1248 21

We have shown that the capacity for local release of tissue-type plasminogen activator (tPA) from the vascular endothelium is impaired in patients with primary hypertension. Because this response is an important protective mechanism against intravascular clotting, we investigated whether this system is also defective in patients with advanced chronic kidney disease and hypertension. Nine nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration rate 11 to 28 mL/min x 1.73 m2; aged 33 to 75 years) were compared with age-matched healthy controls. Intraarterial infusions of desmopressin, methacholine, and sodium nitroprusside were given locally in the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography and blood collected repeatedly during the desmopressin infusion for determination of stimulated net and total cumulated release of tPA. The maximal release rate of active tPA (P<0.05) and the capacity for acute tPA release were markedly impaired in the renal patients as compared with healthy subjects (ANOVA, P=0.013). Accordingly, the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue, respectively (P<0.05). However, there were no significant differences in vasodilator responses between the groups. Thus, patients with advanced chronic kidney disease and hypertension have a markedly impaired capacity for acute release of tissue plasminogen activator, despite preserved endothelium-dependent vasodilation. This defect may contribute to a defective local defense against arterial thrombosis.
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PMID:Impaired endothelial release of tissue-type plasminogen activator in patients with chronic kidney disease and hypertension. 1524 48

Essential arterial hypertension often predisposes patients to prothrombotic state and increased risk of vascular and organ complications. Vital role in regulation of hemostatic processes is played by genetic factors, renin-angiotensin system and disorders of lipid metabolism. Prime genetic factors involved in the process are 4G/5G polymorphism of promoter region coding tissue plasminogen activator inhibitor-1 (PAI-1) and I/D polymorphism for angiotensin converting enzyme (ACE) gene. The aim of work was the evaluation of alterations within fibrinolysis system (estimation of t-PA and PAI-1 levels), fibrinogen concentration (Fb) and ACE activity with regard to co-existent dyslipidemia and features of left ventricle hypertrophy (LVH). Moreover the analysis of influence of 4G/5G PAI and I/D ACE gene polymorphism on intensification of aforementioned alterations among hypertensive patients was performed. Research was carried out in 170 subjects under 40 years old, in two study groups, HT-- hypertensive group--125 patients with previously untreated hypertension without clinical features of ischaemic heart disease and NT--45 normotensive, healthy subjects. HT group has been further divided into four subgroups: DLP (dyslipidemic, n = 51), NLP (normolipidemic n = 74), LVH+ (with features of left ventricle hypertrophy, n = 35), LVH (-) (without features of left ventricle hypertrophy, n = 90). In a whole HT group significantly higher levels of PAI-1, t-PA and Fb were noted in comparison to NT group, considerably more pronounced within DLP rather than NLP subgroups. Moreover, pronounced increase in ACE activity was recorded in DLP and LVH+ subgroups. It has been proved that 4G/4G homozygous subjects of 4G/5G PAI-1 gene polymorphism from HT group tend to present higher levels of PAI-1 and t-PA if contrasted to 4G/4G genotype of NT group, with more distinct effect within DLP subgroup. Carriers of D allele (genotypes I/D, D/D) of I/D ACE gene polymorphism from HT group characterise with significantly higher activity of ACE in contrast to I/I genotype of HT group, with particularly marked effect in DLP and LVH+ subgroups. Basing on above mentioned results it may be concluded that essential hypertension (especially if complicated with dyslipidemia) impairs fibrinolysis, what might be related to renin-angiotensin system activation in lipid metabolism disorders. Deletion alleles of 4G/5G polymorphism (4G allele) and I/D polymorphism (D allele) in patients with hypertension independently modify fibrinolysis towards prothrombotic state with more distinct effect in dyslipidemia. Increased activity of ACE in D allele carriers may predispose to left ventricle hypertrophy.
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PMID:[Plasminogen activator inhibitor-1 (PAI-1) 4G/5G and angiotensin converting enzyme (ACE) I/D gene polymorphisms and fibrinolytic activity in patients with essential hypertension and dyslipidemia]. 1613 May 96

The aim of our study was to evaluate potential differences in the concentration of biochemical markers of endothelial dysfunction between essential hypertension, endocrine hypertension (pheochromocytoma, primary hyperaldosteronism) and control healthy group and to assess a potential relationship between these markers of endothelial dysfunction and vasopressor substances overproduced in endocrine hypertension. We have investigated 21 patients with moderate essential hypertension, 29 patients with primary hyperaldosteronism, 24 subjects with pheochromocytoma and 26 healthy volunteers. Following parameters of endothelial dysfunction were measured, von Willebrand factor (vWf), plasminogen activator (t-PA) and E-selectin (E-sel). Clinical blood pressure was measured according to the European Society of Hypertension recommendations. We found significantly higher levels of the von Willebrand factor in patients with essential hypertension in comparison with a control group (114+/-20 IU/dl vs 90+/-47 IU/dl; P=0.04) and patients with primary hyperaldosteronism (114+/-20 IU/dl vs 99+/-11 IU/dl; P=0.01). Patients with endocrine hypertension revealed increased levels of vWF compared to the control group, but these differences did not reach statistical significance. Levels of t-PA were increased in patients with pheochromocytoma in comparison with the control group (4.6+/-1.9 ng/ml vs 3.4+/-0.9 ng/ml; P=0.01) and with primary hyperaldosteronism (4.6+/-1.9 ng/ml vs 3.4+/-1.1 ng/ml; P<0.01). In case of E-selectin we found lower levels in patients with pheochromocytoma in comparison with other groups, but they differed significantly only with primary hyperaldosteronism (40.2+/-15.0 ng/ml vs 51.3+/-23.0 ng/ml; P=0.05). Our study did not reveal any convincing evidence of differences in the levels of biochemical markers of endothelial dysfunction between essential and endocrine hypertension. No correlation between the biochemical markers of endothelial dysfunction and vasopressor substances activated in endocrine hypertension was found.
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PMID:Biochemical markers of endothelial dysfunction in patients with endocrine and essential hypertension. 1649 5

The increased risk for myocardial infarction and ischemic stroke in primary hypertension suggests that the condition is associated with prothrombotic mechanisms. We have shown that patients with hypertension have an impaired capacity for acute endothelial tissue-type plasminogen activator (t-PA) release, an important local protective response to prevent formation of intravascular thrombi. The aim of the present study was to investigate whether this impairment could be restored by the lowering of blood pressure. The capacity for acute t-PA release in response to intraarterial infusion of substance P at 8 pmol/min was investigated in a perfused-forearm study in 20 hypertensive patients (12 men and 8 women). Studies were performed when patients were untreated and after 8 weeks of randomized treatment with lisinopril or felodipine that lowered blood pressure by 26/10 and 24/12 mm Hg, respectively. The t-PA release response increased significantly with treatment (ANOVA, P=0.0001), with a similar effect in the 2 treatment groups. The peak release of t-PA increased from 257 (58) to 445 (77) ng/min x L/tissue(-1) (t test, P=0.02). Also, treatment shortened the average time to peak secretion from 6.7 (1.4) to 2.7 (0.3) min (t test, P=0.01). In 6 patients with a delayed secretory peak (9 minutes or later), treatment normalized the response (chi2 test, P=0.008). Antihypertensive therapy restores the capacity for acute t-PA release and improves the rapidity of the response in patients with primary hypertension. Similar responses with the 2 regimens suggest that the improvement is related to the blood pressure reduction as such. This effect may contribute to the thromboprotective effect of antihypertensive treatment.
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PMID:Impaired capacity for stimulated fibrinolysis in primary hypertension is restored by antihypertensive therapy. 1652 Apr 4

We evaluated the possible role of NO in modulating tissue plasminogen activator (t-PA) release in the forearm microcirculation of normotensive subjects and hypertensive patients. Essential hypertensive patients are characterized by endothelial dysfunction because of a reduced NO availability and also show an impaired t-PA release. In healthy volunteers and essential hypertensive patients, we studied local t-PA release and forearm blood flow changes (strain-gauge plethysmography) induced by intrabrachial administration of acetylcholine (0.45 and 1.5 microg/100 mL/min) and of sodium nitroprusside (0.5 and 1.0 microg/100 mL/min), an endothelium-dependent and -independent agonist, respectively. Acetylcholine was also repeated in the presence of intra-arterial infusion of the NO synthase inhibitor N(G)-monomethyl-l-arginine (100 microg/100 mL/min). In normotensive subjects, vasodilation to acetylcholine was blunted by N(G)-monomethyl-l-arginine. In these subjects, acetylcholine infusion induced a significant, dose-dependent increase in net forearm t-PA release. N(G)-monomethyl-l-arginine significantly reduced basal t-PA release, as well as acetylcholine-induced t-PA release. In essential hypertensive patients, vasodilation to acetylcholine was reduced as compared with controls and resistant to N(G)-monomethyl-l-arginine. In contrast to what was observed in healthy control subjects, in hypertensive patients, acetylcholine had no effect on t-PA release. Similarly, N(G)-monomethyl-l-arginine failed to modify either the tonic or the agonist-induced t-PA release. Both tonic and agonist-induced release of NO are directly involved in t-PA release by endothelial cells. Essential hypertension, characterized by a reduction in tonic and stimulated NO availability, is also associated with impaired capacity of t-PA release, suggesting a major role of impaired NO availability in worsening both vasodilation and t-PA release.
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PMID:Nitric oxide modulates tissue plasminogen activator release in normotensive subjects and hypertensive patients. 1733 40

The aim of this study was to evaluate the fibrinolytic system by measurement of fibrinogen, plasminogen, tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) in healthy normotensive subjects and in patients with essential hypertension. A group of 21 healthy normotensive subjects [age, 39.2 +/- 1.8 years; 8 males, 13 females; body mass index (BMI) = 27.9 kg/m] and 42 patients with untreated essential hypertension (age, 47.6 +/- 1.7 years; 19 males, 23 females; BMI = 28.3 kg/m) were studied. Blood samples and clinical measurement were taken between 7 am and 9 am by an observer in a blind fashion. The systolic/diastolic blood pressure of normotensive subjects was 121.3 +/- 2.5/78.4 +/- 1.3 mm Hg and that of hypertensive patients was 166.4 +/- 4.3/102.9 +/- 1.83 mm Hg, measured in the sitting position. Plasma fibrinogen levels in the normotensive and hypertensive individuals were 295.7 +/- 9.4 mg/dL and 305.67 +/- 10.9 mg/dL, respectively (P = 0.456). The corresponding values for plasminogen were 71.4 +/- 3.8% and 89.5 +/- 2.5%, (P = 0.0031), for t-PA were 6.3 +/- 0.5 ng/mL and 7.6 +/- 0.4 ng/mL (P = 0.0487), and for PAI-1 were 46.9 +/- 5.1 ng/mL and 63.0 +/- 5.6 ng/mL (P = 0.0324), respectively. In conclusion, patients with essential hypertension have disequilibrium in the fibrinolytic system with a tendency toward a hypercoagulability state when compared with normotensive subjects. This state could explain, in part, the thrombotic complications that occur with a higher frequency in hypertensive patients as compared with normotensive subjects.
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PMID:Fibrinolytic system in normotensive subjects and hypertensive patients. 1741 87

Postprandial hypertriglyceridemia is associated with a series of atherogenic abnormalities, including a prothrombotic state and inflammation. Hypertensive patients have exaggerated postprandial triglyceride response. The benefit of combined treatment of statin and angiotensin II type 1 receptor blocker (ARB) has been demonstrated in diabetic patients. The aim of this investigation was to explore the effect of a statin, fluvastatin, and the ARB valsartan, alone and in combination, on fibrinolytic activity and inflammation after a high-fat meal in patients with essential hypertension (EHP). A total of 53 EHP patients were studied. The concentrations of plasma lipid profiles, soluble P-selectin, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type I (PAI-1) antigens were measured in fasting state and at 4 hours after a single high-fat meal (800 calories; 50 g fat). Patients randomly accepted placebo, fluvastatin 40 mg/day, valsartan 80 mg/day, or both for 1 week. Then a high-fat meal and assay of plasma samples were repeated. The postprandial plasma triglyceride, soluble P-selectin, PAI-1, and t-PA antigen concentrations significantly increased after a high-fat meal. Postprandial plasma concentration of triglyceride was significantly correlated with that of soluble P-selectin and PAI-1 antigen, respectively (P<0.001). The postprandial increase in plasma P-selectin, PAI-1, and t-PA antigen levels was attenuated by 1-week fluvastatin-alone and valsartan-alone treatments; their combination is more effective on both fasting and postprandial P-selectin, plasma PAI-1, and t-PA antigen levels. The improvement of these plasma variables was not significantly related to the changes of plasma lipids and blood pressure. In conclusion, postprandial hypertriglyceridemia induces postprandial fibrinolytic dysfunction and vascular inflammation in patients with essential hypertension after a high-fat meal. Short-term combined treatment with fluvastatin and valsartan more effectively inhibits this postprandial atherogenic change in plasma than monotherapy.
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PMID:Effect of fluvastatin and valsartan, alone and in combination, on postprandial vascular inflammation and fibrinolytic activity in patients with essential hypertension. 1766 15

The relationship between adrenergic stimuli and NO in modulating tissue-type plasminogen activator (t-PA) release from endothelial cells was investigated in normotensive subjects and essential hypertensive patients. Sympathetic activation, a well-known stimulus for endogenous fibrinolysis, is also involved in the determination of cardiovascular risk in essential hypertension. However, the existence of cross-talk between adrenergic stimuli and NO availability in modulating t-PA release is not well established yet. We assessed the release of t-PA in the forearm microcirculation of 58 normotensive subjects (mean age: 47+/-9 years) and 44 essential hypertensive patients (mean age: 48+/-11 years) under specific intra-arterial adrenergic stimuli. Intrabrachial infusion of epinephrine (0.1 to 0.3 microg/100 mL per minute) induced greater t-PA release in normotensive subjects as compared with essential hypertensive patients (P<0.05). However, inhibition of NO synthase with N(G)-monomethyl-L-arginine (100 microg/100 mL per minute) infusion blunted epinephrine-induced t-PA release in normotensive subjects (P<0.05) but not in essential hypertensive patients. In normotensive subjects, t-PA release by epinephrine was not affected by phentolamine (8 microg/100 mL per minute) coinfusion and was abolished in the presence of propanolol (10 microg/100 mL per minute). Intrabrachial isoproterenol (0.03 microg/100 mL per minute) induced a significant increase in t-PA release (P<0.01), an effect blunted by N(G)-monomethyl-L-arginine (P<0.05). In essential hypertensive patients, the response to isoproterenol was impaired as compared with normotensive subjects and was unaffected by N(G)-monomethyl-L-arginine coinfusion. In conclusion, the results of the present study demonstrate that adrenergic-induced t-PA release is mediated by beta-adrenoreceptors via a mechanism involving the NO pathway. Our results show an impaired adrenergic-stimulated t-PA release among essential hypertensive patients, probably mediated via a reduced NO availability. This impaired fibrinolytic activity might contribute to the increased cardiovascular risk associated with hypertension.
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PMID:Tissue-type plasminogen activator release in healthy subjects and hypertensive patients: relationship with beta-adrenergic receptors and the nitric oxide pathway. 1857 69


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