Several plasminogen activators (PAs) have been found effective in treating different thromboembolic diseases. However, administration of conventional thrombolytic therapy is limited by a low efficacy of present formulations of PAs. Conventional treatments using these therapeutic proteins are associated with several limitations including rapid inactivation and clearance, short half-life, bleeding complications or non-specific tissue targeting. Liposome-based formulations of PAs such as streptokinase, tissue-plasminogen activator and urokinase have been developed to improve the therapeutic efficacy of these proteins. Resulting liposomal formulations were found to preserve the original activity of PAs, promote their selective delivery and improve thrombus targeting. Therapeutic potential of these liposome-based PAs has been demonstrated successfully in various pre-clinical models in vivo. Reductions in unwanted side effects (e.g., hemorrhage or immunogenicity) as well as enhancements of efficacy and safety were achieved in comparison to currently existing treatment options based on conventional formulations of PAs. This review summarizes present achievements in: (i) preparation of liposome-based formulations of various PAs, (ii) development of PEGylated and targeted liposomal PAs, (iii) physico-chemical characterization of these developed systems, and (iv) testing of their thrombolytic efficacy. We also look to the future and the imminent arrival of theranostic liposomal formulations to move this field forward.

• Klíčová slova
• Fibrin, Liposomes, Platelets, Protein delivery, RGD peptide, Streptokinase, Stroke, Thrombus, Tissue plasminogen activator, Urokinase,
• MeSH
• aktivátor plazminogenu urokinázového typu aplikace a dávkování   terapeutické užití   MeSH
• fibrinolytika aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• liposomy chemie   ultrastruktura   MeSH
• metaloendopeptidasy aplikace a dávkování   terapeutické užití   MeSH
• nanostruktury chemie   ultrastruktura   MeSH
• plasmin aplikace a dávkování   terapeutické užití   MeSH
• streptokinasa aplikace a dávkování   terapeutické užití   MeSH
• tkáňový aktivátor plazminogenu aplikace a dávkování   terapeutické užití   MeSH
• tromboembolie farmakoterapie   MeSH
• trombolytická terapie metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH
• auR protein, Staphylococcus aureus MeSH Prohlížeč
• fibrinolytika MeSH
• liposomy MeSH
• metaloendopeptidasy MeSH
• plasmin MeSH
• streptokinasa MeSH
• tkáňový aktivátor plazminogenu MeSH

In order to elucidate the mechanisms of plasminogen activator release into the circulation during the first minutes of experimental myocardial ischaemia in vitro, isolated rat hearts were perfused under optimal conditions and under conditions inducing myocardial ischaemia. In ventricular tissues the content of plasminogen a activator was measured; in the perfusate the plasminogen activator and anticoagulating activities were determined. Under optimal conditions the plasminogen activator content in contracting heart was found to be essentially the same as under in vivo conditions; in the perfusates the release of plasminogen activator and of substances possessing the anticoagulating activity was insignificant. Under myocardial ischaemia the release of these substances into the circulation increased, while plasminogen activator content decreased.

• MeSH
• aktivátory plazminogenu metabolismus   MeSH
• fibrinolýza MeSH
• koronární nemoc metabolismus   MeSH
• krysa rodu Rattus MeSH
• myokard metabolismus   MeSH
• techniky in vitro MeSH
• zmrazování MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aktivátory plazminogenu MeSH

Tick saliva is a rich source of modulators of vascular biology. We have characterized Ixonnexin, a member of the "Basic-tail" family of salivary proteins from the tick Ixodes scapularis. Ixonnexin is a 104 residues (11.8 KDa), non-enzymatic basic protein which contains 3 disulfide bonds and a C-terminal rich in lysine. It is homologous to SALP14, a tick salivary FXa anticoagulant. Ixonnexin was produced by ligation of synthesized fragments (51-104) and (1-50) followed by folding. Ixonnexin, like SALP14, interacts with FXa. Notably, Ixonnexin also modulates fibrinolysis in vitro by a unique salivary mechanism. Accordingly, it accelerates plasminogen activation by tissue-type plasminogen activator (t-PA) with Km 100 nM; however, it does not affect urokinase-mediated fibrinolysis. Additionally, lysine analogue ε-aminocaproic acid inhibits Ixonnexin-mediated plasmin generation implying that lysine-binding sites of Kringle domain(s) of plasminogen or t-PA are involved in this process. Moreover, surface plasmon resonance experiments shows that Ixonnexin binds t-PA, and plasminogen (KD 10 nM), but not urokinase. These results imply that Ixonnexin promotes fibrinolysis by supporting the interaction of plasminogen with t-PA through formation of an enzymatically productive ternary complex. Finally, in vivo experiments demonstrates that Ixonnexin inhibits FeCl3-induced thrombosis in mice. Ixonnexin emerges as novel modulator of fibrinolysis which may also affect parasite-vector-host interactions.

• MeSH
• arteriální okluzní nemoci chemicky indukované   patologie   prevence a kontrola   MeSH
• chloridy toxicita   MeSH
• fibrinolýza účinky léků   MeSH
• klíšťata metabolismus   MeSH
• myši MeSH
• noxy toxicita   MeSH
• plazminogen metabolismus   MeSH
• slinné proteiny a peptidy farmakologie   MeSH
• sliny metabolismus   MeSH
• tkáňový aktivátor plazminogenu metabolismus   MeSH
• trombóza chemicky indukované   patologie   prevence a kontrola   MeSH
• železité sloučeniny toxicita   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• chloridy MeSH
• ferric chloride MeSH Prohlížeč
• noxy MeSH
• plazminogen MeSH
• slinné proteiny a peptidy MeSH
• tkáňový aktivátor plazminogenu MeSH
• železité sloučeniny MeSH

Plasminogen activator inhibitor-1 (PAI-1) impedes brain plasmin synthesis. Reduced plasmin activity facilitates cumulation of amyloid beta (Aβ) in Alzheimer's disease (AD). Since plasmin also regulates the synaptic activity, it is possible that altered PAI-1 is present in other neurodegenerative disorders. We investigated whether PAI-1 and its counter-regulatory tissue plasminogen activator (tPA) are altered in serum of patients with dementia due to frontotemporal lobar degeneration (FTLD). Thirty five FTLD patients (21 in mild cognitive impairment stage (MCI) and 14 in dementia stage) and 10 cognitively healthy controls were recruited. Serum tPA and PAI-1 protein levels were measured by anova. Correlation between biochemical and demographic data were explored by measuring Pearson correlation coefficient. Serum PAI-1 levels were elevated in the FTLD dementia group as compared to FTLD MCI and controls. tPA serum levels and PAI-1/tPA ratio did not significantly differ among groups. There was a negative correlation between PAI-1 serum levels and disease severity measured by MMSE score. No correlations of tPA serum levels and PAI-1/tPA ratio with MMSE were found. Increased PAI-1 serum levels may serve as a marker of dementia in FTLD, suggesting that, besides Aβ pathway, the plasmin system may affect cognition through synaptic activity.

• Klíčová slova
• dementia, frontotemporal lobar degeneration, plasminogen activator inhibitor‐1, tissue‐type plasminogen activator,
• MeSH
• biologické markery krev   MeSH
• frontotemporální lobární degenerace * krev   MeSH
• inhibitor aktivátoru plazminogenu 1 * krev   MeSH
• kognitivní dysfunkce krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tkáňový aktivátor plazminogenu krev   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• inhibitor aktivátoru plazminogenu 1 * MeSH
• SERPINE1 protein, human MeSH Prohlížeč
• tkáňový aktivátor plazminogenu MeSH

PURPOSE: To investigate the prognostic role of expression of urokinase-type plasminogen activator system members, such as urokinase-type activator (uPA), uPA-receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). METHODS: Immunohistochemical staining for uPA system was performed on a tissue microarray of specimens from 3121 patients who underwent RP. Cox regression analyses were performed to investigate the association of overexpression of these markers alone or in combination with biochemical recurrence (BCR). Decision curve analysis was used to assess the clinical impact of these markers. RESULTS: uPA, uPAR, and PAI-1 were overexpressed in 1012 (32.4%), 1271 (40.7%), and 1311 (42%) patients, respectively. uPA overexpression was associated with all clinicopathologic characteristics of biologically aggressive PCa. On multivariable analysis, uPA, uPAR, and PAI-1 overexpression were all three associated with BCR (HR: 1.75, p < 0.01, HR: 1.22, p = 0.01 and HR: 1.20, p = 0.03, respectively). Moreover, the probability of BCR increased incrementally with increasing cumulative number of overexpressed markers. Decision curve analysis showed that addition of uPA, uPAR, and PAI-1 resulted in a net benefit compared to a base model comparing standard clinicopathologic features across the entire threshold probability range. In subgroup analyses, overexpression of all three markers remained associated with BCR in patients with favorable pathologic characteristics. CONCLUSION: Overexpression of uPA, uPAR, and PAI-1 in PCa tissue were each associated with worse BCR. Additionally, overexpression of all three markers is informative even in patients with favorable pathologic characteristics potentially helping clinical decision-making regarding adjuvant therapy and/or intensified follow-up.

• Klíčová slova
• Biochemical recurrence, Prostate cancer, Radical prostatectomy, Urokinase-type plasminogen activator,
• MeSH
• aktivátor plazminogenu urokinázového typu biosyntéza   fyziologie   MeSH
• inhibitor aktivátoru plazminogenu 1 biosyntéza   fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru epidemiologie   etiologie   MeSH
• nádorové biomarkery biosyntéza   fyziologie   MeSH
• nádory prostaty epidemiologie   etiologie   metabolismus   chirurgie   MeSH
• prognóza MeSH
• prostatektomie * MeSH
• receptory urokinázového aktivátoru plazminogenu biosyntéza   fyziologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH
• inhibitor aktivátoru plazminogenu 1 MeSH
• nádorové biomarkery MeSH
• PLAUR protein, human MeSH Prohlížeč
• receptory urokinázového aktivátoru plazminogenu MeSH
• SERPINE1 protein, human MeSH Prohlížeč

• MeSH
• aktivátor plazminogenu urokinázového typu metabolismus   MeSH
• aktivátory plazminogenu metabolismus   MeSH
• endopeptidasy metabolismus   MeSH
• lidé MeSH
• protrombin metabolismus   MeSH
• tkáňový faktor metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH
• aktivátory plazminogenu MeSH
• endopeptidasy MeSH
• protrombin MeSH
• tkáňový faktor MeSH

Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, a serine protease participating in the activation of matrixmetaloproteinases, latent elastases, growth factors and cytokines involved in the degradation of extracellular matrix elements. Together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI-1, PAI-2, PAI-3 and protease nexin), it forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. Plasminogen activator inhibitor 1 inhibits uPA-dependent invasiveness of some cancer cell lines. The vitronectin-PAI-1 complex inhibits migration of smooth muscle cells by binding alpha(v)beta3 integrin to vitronectin. PAI-1 or its deficiency interferes with signalling pathways such as PI3K/Akt and JAK/STAT and it is included in the processes of maintaining the integrity of the endothelial cells and thereby regulation of cell death. PAI-1 affects apoptosis by reducing cell adhesion and functioning of intracellular signalling pathways. The individual components of PAS undoubtedly play an important role in angiogenesis and metastasising of malignant tumours. In the near future, results of published studies with various types of cancer could be reflected in diagnostic and therapeutic algorithms and, at the same time, could serve as the goal for targeted therapies.

• MeSH
• aktivátor plazminogenu urokinázového typu fyziologie   MeSH
• aktivátory plazminogenu fyziologie   MeSH
• fibrinolýza fyziologie   MeSH
• inhibitor aktivátoru plazminogenu 1 fyziologie   MeSH
• inhibitor aktivátoru plazminogenu 2 MeSH
• lidé MeSH
• nádory patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH
• aktivátory plazminogenu MeSH
• inhibitor aktivátoru plazminogenu 1 MeSH
• inhibitor aktivátoru plazminogenu 2 MeSH

Ligneous membranitis/conjunctivitis (LM, OMIM 217090) is a hereditary disorder caused by a congenital plasminogen (PLG) deficiency. In veterinary medicine, LM (OMIA 002020-9615) has rarely been reported in Golden Retrievers, Yorkshire Terriers, Doberman Pinschers and Scottish Terriers. In the latter breed, an A>T variation in an intron donor site of the PLG gene (PLG, c.1256+2T>A) has been found to be the sole causative molecular defect reported to date in dogs. Owing to the absence of plasmin enzymatic clearance which in turn depends on the lack of its proenzyme plasminogen, fibrin deposits tend to accumulate in viscous membranes on the eyes, triggering and sustaining an intense inflammatory response. A case of LM was diagnosed in a 7-month-old male Maltese dog. The dog was examined for severe recurrent conjunctivitis. A diagnosis of ligneous conjunctivitis was made by an ophthalmologist after a thorough eye examination and was confirmed by a complete lack of plasma activity of plasminogen. The main local signs were redness of the conjunctiva with persistent membranes having ligneous (wood-like) membranes on the eyes. The disease was associated with a complex rearrangement involving the plasminogen gene loci, causing the complete deletion of exon 1. This study provides a spontaneous animal model for LM associated with complete plasminogen deficiency and provides a method for detecting affected or carrier dogs.

• Klíčová slova
• animal model, complex rearrangement, deletion, dog, hereditary disease, ligneous membranitis, ophthalmology, plasminogen,
• MeSH
• chov MeSH
• genetická onemocnění kůže genetika   veterinární   MeSH
• konjunktivitida genetika   veterinární   MeSH
• nemoci psů genetika   MeSH
• plazminogen nedostatek   genetika   MeSH
• psi genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• psi genetika   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• plazminogen MeSH

Haemodialysis (HD) is associated with stimulation of the fibrinolytic system. The increase of fibrinolytic activity seems to be primarily due to tissue-type plasminogen activator (t-PA) released from the vessel wall. The aim of our study was to determine whether the t-PA release is the consequence of uraemic intoxication adjustment, extracorporeal circulation effect, heparin administration, or whether a mere reflection of the circadian rhythm of fibrinolysis is involved. To identify the factor, fibrinolytic system parameters were determined during HD, sham HD (SD), after the administration of heparin alone outside HD, and during a control period (CP). The plasma concentrations of t-PA antigen indicate that HD is associated with the release of t-PA from the vessel wall; 3.70 ng/ml before HD, 4.35 (NS) at the 15th min, 4.88 (P less than 0.05) at the 20th min, and 5.09 (P less than 0.05) after HD (medians). The respective values for a CP are 4.05, 4.37 (NS), 4.40 (NS), and 4.22 (NS). The effect of heparin alone and SD was evaluated for 120 min only, with the following t-PA concentrations determined after heparin: 5.10, 6.22 (NS), 4.72 (NS), 4.72 (NS); during SD and 4.50, 5.14 (NS), 5.20 (P less than 0.05). We conclude that t-PA is released from the vessel wall during HD. A factor contributing to its release is the extracorporeal circulation system.

• MeSH
• cévy metabolismus   MeSH
• chronické selhání ledvin krev   terapie   MeSH
• dialýza ledvin škodlivé účinky   MeSH
• dospělí MeSH
• fibrinolýza MeSH
• lidé MeSH
• tkáňový aktivátor plazminogenu krev   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• tkáňový aktivátor plazminogenu MeSH

• MeSH
• dospělí MeSH
• koagulační faktory * MeSH
• lidé středního věku MeSH
• lidé MeSH
• plazminogen metabolismus   MeSH
• techniky in vitro MeSH
• tkáňové extrakty MeSH
• vena saphena MeSH
• vény * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• koagulační faktory * MeSH
• plazminogen MeSH
• tkáňové extrakty MeSH