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)

Increased sympathetic activity seems to play an important role in the pathogenesis and development of complications of atherosclerotic origin in patients with essential hypertension (EH). The aim of this study was to evaluate the effect of a new antihypertensive agent, moxonidine (M), on microalbuminuria (urine albumin excretion, UAE), plasma thrombomodulin (TM), and tissue plasminogen activator inhibitor (PAI-1) in patients with mild to moderate EH associated with increased UAE. Fifty-eight patients (32 M, 26 F) with EH and microalbuminuria, with a mean age of 56.6 +/- 8.2 years and a body mass index (BMI) of 23.8 +/- 3.1 kg/m2 who responded to M therapy (0.3-0.4 mg/daily) were studied before and after their blood pressure control. The 24-hour urine albumin excretion (RIA method), as well as TM and PAI-1 plasma levels (ELISA method), were determined before and 6 months after the initiation of treatment under moxonidine therapy. At the end of the 6-month period, all patients remained normotensive. The 24-hour urine albumin excretion had decreased to 24.5 +/- 6.4 vs. 32.3 +/- 7.2 ug/min before therapy (P < 0.001). The plasma TM levels had decreased to 44.0 +/- 7 vs. 51.0 +/- 9 ng/mL before therapy (P < 0.01), and PAI-1 levels had also decreased to 11.5 +/- 4.5 vs. 15.8 +/- 8 IU/mL before therapy (P < 0.05). The results of our study suggest that in hypertensive patients with microalbuminuria, moxonidine, an imidazoline I1-receptor agonist, a new centrally acting antihypertensive agent, significantly reduces urine albumin excretion as well as thrombomodulin and PAI-1 levels. These preliminary findings demonstrate a favorable effect on renal function and endothelial homeostatic mechanisms (maintenance of haemostatic balance).
Cardiovasc Drugs Ther 1998 Oct
PMID:Moxonidine effect on microalbuminuria, thrombomodulin, and plasminogen activator inhibitor-1 levels in patients with essential hypertension. 992 77

Compared with primary angioplasty [percutaneous transluminal coronary angioplasty (PTCA)], rescue PTCA is associated with lower angiographic success and higher reocclusion rates, especially after thrombolysis with tissue-type plasminogen activator (tPA). Although stent placement during primary PTCA has been demonstrated to be safe and even to improve the angiographic results achieved by balloon-alone PTCA, there are few data on stent placement during rescue PTCA after failed thrombolysis. This study sought to assess the feasibility and safety of stent implantation during rescue angioplasty in myocardial infarction after failed thrombolysis. The study population consisted of 20 patients with acute myocardial infarction referred for rescue PTCA after failed thrombolysis consecutively treated with coronary stenting. The thrombolytic agent was tPA in 15 patients (75%), streptokinase in 1 (5%), and anisoylated streptokinase plasminogen activator complex (APSAC) in 1 (5%); 3 patients (15%) were included in the INTIME II study (tPA vs. lanoteplase). After stenting, aspirin 200 mg daily plus ticlopidine 250 mg b.i.d. were administered. Thirty stents (1.5+/-1.0 per patient) were implanted. Angiographic success was achieved in 19 patients (95%). Two patients (10%) died, both because of severe bleeding complications. One patient (5%) suffered a reinfarction, but no patients suffered postinfarction angina or needed new target vessel revascularization. Eighteen patients (90%) were discharged alive and free of events. All these patients remained asymptomatic and free of target vessel revascularization at 6-month follow-up. Stent placement during rescue PTCA after failed thrombolysis is feasible and safe and is associated with a good angiographic result and clinical outcome. Bleeding complications seem to be, however, the main limitation of this reperfusion strategy.
Catheter Cardiovasc Interv 1999 May
PMID:Coronary stenting during rescue angioplasty after failed thrombolysis. 1038 50

In the 13 years since the publication of the GISSI-1 study in 1986, and the incorporation of thrombolysis into the standard management of myocardial infarction, this treatment has, apparently, fulfilled its promise. Short-term mortality gains are accompanied by improvements in ventricular function and a reduction in major cardiovascular complications. Follow-up studies have demonstrated that these short-term gains, following a single thrombolytic administration, are sustained for at least 8 years with persistent separation of the survival curves. In terms of cost effectiveness, this is a remarkable success. Streptokinase and accelerated tPA administration are the most widely used thrombolytic agents, and yet only about 50% of patients achieve unrestricted flow (TIMI 3) within 90 minutes of administration. Newer agents, including genetically modified tPA and a much older agent, staphylokinase, appear to offer superior patency rates and simpler administration. However, bleeding risks remain a concern and cannot be predicted from smaller scale studies. This lesson has been learned from the attempts to augment heparin or other antithrombotic treatment in conjunction with thrombolysis, resulting in increased rates of major and cerebral bleeding. We have not reached the limit in applying thrombolysis to all potentially eligible patients. By doing so, with a minimum of delay, more lives would be saved than by substitution of thrombolytic agents or by using adjunctive treatments with marginal survival advantages.
Cardiovasc Drugs Ther 1999 May
PMID:Have we reached the limit with thrombolytic therapy? 1043 83

We report a case of tissue plasminogen activator-associated spinal epidural hematoma in a patient who underwent treatment for myocardial infarction. Diagnostic magnetic resonance imaging was used within 24 hr of coronary artery stent implantation. We review the literature on thrombolytic-associated epidural spinal hematoma and discuss its management. Cathet. Cardiovasc. Intervent. 48:390-396, 1999.
Catheter Cardiovasc Interv 1999 Dec
PMID:Spinal epidural hematoma associated with tissue plasminogen activator treatment of acute myocardial infarction. 1055 22

The enzymatic cascade triggered by activation of plasminogen has been implicated in a variety of normal and pathologic events, such as fibrinolysis, wound healing, tissue remodeling, embryogenesis, and the invasion and spread of transformed tumor cells. Recent data established that the Ca(2+)- and phospholipid-binding protein, annexin II heterotetramer (AIIt) binds tissue-type plasminogen activator (tPA), plasminogen, and plasmin, and dramatically stimulates the tPA-dependent conversion of plasminogen to plasmin in vitro. Interestingly, the binding of plasmin to AIIt can inhibit the activity of the enzyme, suggesting that plasmin bound to the cell surface is regulated by AIIt. The existing experimental evidence suggests that AIIt is the key physiological receptor for plasminogen on the extracellular surface of endothelial cells.
Trends Cardiovasc Med
PMID:Role of annexin II tetramer in plasminogen activation. 1057 24

A 76-year-old woman receiving warfarin after aortic valve replacement experienced prosthetic valve thrombosis during dicloxacillin therapy. Successful thrombolysis was achieved with tissue plasminogen activator. The international normalized ratio (INR) on admission was reduced to 1.4 and an increased warfarin dosage was required for three weeks following discontinuation of dicloxacillin treatment in order to maintain therapeutic INRs. Careful monitoring of INRs and titration of the warfarin dosage is recommended when dicloxacillin is prescribed to patients receiving warfarin.
Scand Cardiovasc J 1999
PMID:Prosthetic heart valve thrombosis during dicloxacillin therapy. 1062 50

Systemic gene therapy involves the transfer into the body of a gene whose protein product reaches the blood and has a beneficial effect on a patient. Both retroviral and adenovirus-associated viral vectors have resulted in stable but only moderate systemic levels of blood proteins. Adenoviral vectors have resulted in very high levels of expression that diminishes over days or weeks. Hepatic gene therapy has achieved levels of the anticoagulant protein C in blood that would protect against spontaneous thromboses in homozygous protein-C deficiency, and levels of tissue plasminogen activator that can lyse pulmonary emboli. Hypercholesterolemia has been ameliorated transiently by transfer of the low-density lipoprotein receptor gene into the livers of animals with familial hypercholesterolemia or by promoting lipid transfer via a variety of alternative mechanisms. Hypertension has been reduced by the transfer of genes for kallikrein or atrial natriuretic peptide into the liver, or by expressing antisense for the angiotensin II type I receptor after intravenous injection in neonates. Finally, fasting but not fed hyperglycemia has been ameliorated in animal models of diabetes by transfer of an insulin gene into the liver or by expression of insulin from implanted fibroblasts. Gene therapy has the potential to treat these cardiovascular diseases. However, improvements in levels of long-term expression and the ability to regulate expression in response to physiologic changes will be required before this approach will be implemented for most of these disorders in humans.
Trends Cardiovasc Med 1999 Aug
PMID:Systemic gene therapy for cardiovascular disease. 1063 21

The annexins constitute a family of calcium-dependent membrane binding proteins. Recently, annexin II has been shown to accelerate the activation of the clot-dissolving protease plasmin by complexing with the plasmin precursor plasminogen and with tissue plasminogen activator. Binding of plasminogen to annexin II is inhibited by the atherogenic lipoprotein, lipoprotein(a), while binding of tissue plasminogen activator to annexin II is blocked by the thiol amino acid homocysteine. Formation of the plasminogen/tissue plasminogen activator/annexin II complex may represent a key regulatory mechanism in fibrinolytic surveillance.
Trends Cardiovasc Med 1999 Jul
PMID:Annexin II: a mediator of the plasmin/plasminogen activator system. 1063 27

Randomized clinical trials have clearly shown the beneficial effects of early reperfusion within 12 hours, and possibly up to 24 hours, after acute myocardial infarction (AMI). The data on late reperfusion beyond 24 hours are less convincing. Many studies show that an open infarct-related artery after MI, irrespective of the initial reperfusion strategy, is independently associated with improved long-term clinical outcome. However, similar analysis of the large Global Utilization of Streptokinase and tPA for Occluded Arteries (GUSTO) 1 study did not confirm this finding. It is unclear whether mechanical reperfusion of an occluded infarct-related artery late after MI (>24 hours) in asymptomatic patients will confer long-term benefits. The late open artery hypothesis, which proposes several mechanisms by which late reperfusion may offer benefit, remains to be tested in a large clinical trial. This overview focuses on the definitions of early reperfusion, late reperfusion, the relationship between timing of reperfusion and prognosis after AMI, and the late open artery hypothesis.
Prog Cardiovasc Dis
PMID:Early reperfusion, late reperfusion, and the open artery hypothesis: an overview. 1087 Nov 62

We investigated late-onset anastomotic stenosis in an implanted prosthetic graft. Rupture of the pseudointima and hemorrhaging from the vasa vasorum were observed at the border of the collagenous tissue and fibrin layer. An immunohistological study showed that the fibrin layer was positive for tPA, but weakly positive for PAI-1. Some neutrophils and monocyte/macrophages in the fibrin layer were immunostained for tPA, uPA, uPAR, and MMP-1, -2 and -3. Some spindle-shaped cells surrounding the graft were immunostained for uPA, uPAR, MMP-1, -2, -3, -7 and -9, and TIMP-1 and -2. The endothelial cells of some microvessels were positive for MMP-1 and -2, and tPA. Some multi-nucleated giant cells were immunostained for MMP-7 and-9, tPA, PAI-1, uPA, and uPAR. Overexpressed MMPs and PAs possibly caused instability of the pseudointima.
J Cardiovasc Surg (Torino) 2000 Jun
PMID:Rupture of pseudointima in an implanted vascular prosthesis: immunohistological study of plasminogen activators and matrix metalloproteinases. 1095 41


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