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https://www.readbyqxmd.com/read/28740853/prothrombotic-fibrin-clot-phenotype-in-patients-with-deep-vein-thrombosis-and-pulmonary-embolism-a-new-risk-factor-for-recurrence
#1
REVIEW
Anetta Undas
Prothrombotic fibrin clot phenotype, involving faster formation of dense meshwork composed of thinner and highly branched fibers that are relatively resistant to plasmin-induced lysis, has been reported in patients with not only myocardial infarction or stroke, but also venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT), and/or pulmonary embolism (PE). Prothrombotic fibrin clot phenotype, in particular prolonged clot lysis time, is considered a novel risk factor for VTE as well as venous thrombosis at unusual location, for example, cerebral sinus venous thrombosis, retinal vein obstruction, and Budd-Chiari syndrome...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28724633/conformationally-organized-lysine-isosteres-in-streptococcus-pyogenes-m-protein-mediate-direct-high-affinity-binding-to-human-plasminogen
#2
Yue Yuan, Jaroslav Zajicek, Cunjia Qiu, Vishwanatha Chandrahas, Shaun W Lee, Victoria A Ploplis, Francis J Castellino
The binding of human plasminogen (hPg) to the surface of the human pathogen Streptococcus pyogenes (GAS) and subsequent hPg activation to the protease plasmin generate a proteolytic surface that GAS employs to circumvent host innate immunity. Direct high-affinity binding of hPg/plasmin to pattern D GAS is fully recapitulated by the hPg kringle 2 domain (K2hPg) and a short internal peptide region (a1a2) of a specific subtype of bacterial surface M protein, present in all GAS pattern D strains. To better understand the nature of this binding, critical to the virulence of many GAS skin-tropic strains, we used high-resolution NMR to define the interaction of recombinant K2hPg with recombinant a1a2 (VKK38) of the M protein from GAS isolate NS455...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28713823/intracardiac-hemostasis-and-fibrinolysis-parameters-in-patients-with-atrial-fibrillation
#3
Noémi Klára Tóth, Zoltán Csanádi, Orsolya Hajas, Alexandra Kiss, Edina Nagy-Baló, Kitti Bernadett Kovács, Ferenc Sarkady, László Muszbek, Zsuzsanna Bereczky, László Csiba, Zsuzsa Bagoly
AIMS: To identify intracardiac hemostasis or fibrinolysis abnormalities, which are associated with atrial fibrillation (AF) and increase the risk of thromboembolism. PATIENTS AND METHODS: Patient group consisted of 24 patients with AF and control group included 14 individuals with other supraventricular tachycardia undergoing transcatheter radiofrequency ablation. Blood samples were drawn from the femoral vein (FV), left atrium (LA), and left atrial appendage (LAA) before the ablation procedure...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28710283/amorphous-protein-aggregates-stimulate-plasminogen-activation-leading-to-release-of-cytotoxic-fragments-that-are-clients-for-extracellular-chaperones
#4
Patrick Constantinescu, Rebecca A Brown, Amy R Wyatt, Marie Ranson, Mark R Wilson
The misfolding of proteins and their accumulation in extracellular tissue compartments as insoluble amyloid or amorphous protein aggregates is a hallmark feature of many debilitating protein deposition diseases such as Alzheimers disease, prion diseases and type II diabetes. The plasminogen activation system (PAS) is best known as an extracellular fibrinolytic system, but was previously reported to also be capable of degrading amyloid fibrils. Here we show that amorphous protein aggregates interact with tPA and plasminogen, via an exposed lysine dependent mechanism, to efficiently generate plasmin...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28700732/tissue-plasminogen-activator-mediates-deleterious-complement-cascade-activation-in-stroke
#5
Xue-Jun Zhao, Timothy M Larkin, Molly A Lauver, Saif Ahmad, Andrew F Ducruet
The use of intravenous tissue plasminogen activator (tPA) in the treatment of ischemic stroke is limited by its propensity to exacerbate brain edema and hemorrhage. The mechanisms underlying these deleterious effects of tPA remain incompletely understood. The purpose of this study was to delineate a pathway of tPA-mediated complement cascade activation in stroke and to determine whether complement inhibition ameliorates the adverse effects of post-ischemic tPA administration. We found that tPA promotes C3 cleavage both in vitro and in ischemic brain through a plasmin-mediated extrinsic pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28698333/research-protocol-for-platelets-in-out-of-hospital-cardiac-arrest-an-observational-case-controlled-feasibility-study-to-assess-coagulation-and-platelet-function-abnormalities-with-rotem-following-out-of-hospital-cardiac-arrest-pohcar
#6
Agnieszka Skorko, Matthew Thomas, Andrew Mumford, Thomas Johnson, Elinor Griffiths, Rosemary Greenwood, Jonathan Benger
INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) has an annual incidence of approximately 60 000 in the UK. Less than 10% of those who receive resuscitation survive to hospital discharge. For OHCA of a presumed cardiac cause, the optimal antiplatelet therapy is currently unknown. Previous studies indicate that a procoagulopathic state exists postcardiac arrest which may contribute to the formation of thrombi and contribute to poor outcomes. However, the administration of antiplatelet therapies needs to be balanced against the increased risk of bleeding that these individuals face...
July 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28697634/the-fibrinolysis-inhibitor-%C3%AE-2-antiplasmin-restricts-lymphatic-remodelling-and-metastasis-in-a-mouse-model-of-cancer
#7
Sophie Paquet-Fifield, Sally Roufail, You-Fang Zhang, Trifina Sofian, David J Byrne, Paul B Coughlin, Stephen B Fox, Steven A Stacker, Marc G Achen
Remodelling of lymphatic vessels in tumours facilitates metastasis to lymph nodes. The growth factors VEGF-C and VEGF-D are well known inducers of lymphatic remodelling and metastasis in cancer. They are initially produced as full-length proteins requiring proteolytic processing in order to bind VEGF receptors with high affinity and thereby promote lymphatic remodelling. The fibrinolytic protease plasmin promotes processing of VEGF-C and VEGF-D in vitro, but its role in processing them in cancer was unknown...
July 11, 2017: Growth Factors
https://www.readbyqxmd.com/read/28692110/plasma-carboxypeptidase-u-cpu-cpb2-tafia-generation-during-in-vitro-clot-lysis-and-its-interplay-between-coagulation-and-fibrinolysis
#8
Dorien Leenaerts, Jef Aernouts, Pieter Van Der Veken, Yani Sim, Anne-Marie Lambeir, Dirk Hendriks
Carboxypeptidase U (CPU, CPB2, TAFIa) is a basic carboxypeptidase that is able to attenuate fibrinolysis. The inactive precursor procarboxypeptidase U is converted to its active form by thrombin, the thrombin-thrombomodulin complex or plasmin. The aim of this study was to investigate and characterise the time course of CPU generation in healthy individuals. In plasma of 29 healthy volunteers, CPU generation was monitored during in vitro clot lysis. CPU activity was measured by means of an enzymatic assay that uses the specific substrate Bz-o-cyano-Phe-Arg...
July 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28687976/annexin-a2-s100a10-heterotetramer-is-upregulated-by-pml-rar%C3%AE-fusion-protein-and-promotes-plasminogen-dependent-fibrinolysis-and-matrix-invasion-in-acute-promyelocytic-leukemia
#9
Dan Huang, Yan Yang, Jian Sun, Xiaorong Dong, Jiao Wang, Hongchen Liu, Chengquan Lu, Xueyu Chen, Jing Shao, Jinsong Yan
Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor α (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5'-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive...
July 8, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28686706/plasminogen-tochigi-mice-exhibit-phenotypes-similar-to-wild-type-mice-under-experimental-thrombotic-conditions
#10
Yuko Tashima, Fumiaki Banno, Toshiyuki Kita, Yasuyuki Matsuda, Hiroji Yanamoto, Toshiyuki Miyata
Plasminogen (Plg) is a precursor of plasmin that degrades fibrin. A race-specific A620T mutation in Plg, also known as Plg-Tochigi, originally identified in a patient with recurrent venous thromboembolism, causes dysplasminogenemia with reduced plasmin activity. The Plg-A620T mutation is present in 3-4% of individuals in East Asian populations, and as many as 50,000 Japanese are estimated to be homozygous for the mutant 620T allele. In the present study, to understand the changes of thrombotic phenotypes in individuals with the mutant 620T allele, we generated knock-in mice carrying the homozygous Plg-A622T mutation (PlgT/T), an equivalent to the A620T mutation in human Plg...
2017: PloS One
https://www.readbyqxmd.com/read/28684447/plasmin-regulation-of-acute-cytokine-storm
#11
Jesus Maria Gomez-Salinero, Shahin Rafii
No abstract text is available yet for this article.
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28683994/the-effects-of-steroids-on-coagulation-dysfunction-induced-by-cardiopulmonary-bypass-a-steroids-in-cardiac-surgery-sirs-trial-substudy
#12
Domenico Paparella, Alessandro Parolari, Crescenzia Rotunno, Jessica Vincent, Veronica Myasoedova, Pietro Guida, Micaela De Palo, Vito Margari, Philip J Devereaux, Andre Lamy, Francesco Alamanni, Salim Yusuf, Richard Whitlock
Cardiopulmonary bypass (CPB) surgery, despite heparin administration, elicits activation of coagulation system resulting in coagulopathy. Anti-inflammatory effects of steroid treatment have been demonstrated, but its effects on coagulation system are unknown. The primary objective of this study is to assess the effects of methylprednisolone on coagulation function by evaluating thrombin generation, fibrinolysis, and platelet activation in high-risk patients undergoing cardiac surgery with CPB. The Steroids In caRdiac Surgery study is a double-blind, randomized, controlled trial performed on 7507 patients worldwide who were randomized to receive either intravenous methylprednisolone, 250 mg at anesthetic induction and 250 mg at initiation of CPB (n = 3755), or placebo (n = 3752)...
April 2017: Seminars in Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28678111/effectiveness-and-safety-of-batroxobin-tranexamic-acid-and-a-combination-in-reduction-of-blood-loss-in-lumbar-spinal-fusion-surgery
#13
Roopa Mn, Ajoy Prasad Shetty, Srikanth Reddy Dumpa, Balavenkat Subarmaniam, Rishi Mugesh Kanna, Rajasekeran Shanmuganathan
STUDY DESIGN: A prospective randomized double blind placebo controlled trail OBJECTIVE.: To evaluate and compare the efficacy and safety of Batroxobin (botropase),Tranexamic acid(TXA) and their combination in reduction of perioperative blood loss in lumbar spine single level fusion surgeries. SUMMARY OF BACKGROUND DATA: Spinal surgeries are associated with significant blood loss leading to perioperative anaemia and increased need for allogenic transfusion. TXA competitively inhibits plasmin and batroxobin converts fibrinogen to fibrin and theoretically their combination is synergistic ...
July 3, 2017: Spine
https://www.readbyqxmd.com/read/28677806/%C3%AE-2-antiplasmin-modulates-bone-formation-by-negatively-regulating-osteoblast-differentiation-and-function
#14
Yosuke Kanno, Akira Ishisaki, Hiromi Kuretake, Chihiro Maruyama, Ayaka Matsuda, Osamu Matsuo
α2-antiplasmin (α2AP) is known to be a physiological inhibitor of plasmin. Previously, we showed that α2AP displays various functions, such as promotion of extracellular matrix production, cell growth, and cell differentiation that are not promoted by its function as a plasmin inhibitor. We herein investigated the role of α2AP in bone formation by examining calcein incorporation after its injection in α2AP-deficient mice. We found that α2AP deficiency enhanced the bone formation rate in mice. We also found that the osteocalcin expression and alkaline phosphatase activity were elevated in the femur and serum of the α2AP-deficient mice...
July 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28664371/production-purification-and-characterization-of-fibrinolytic-enzyme-from-serratia-sp-kg-2-1-using-optimized-media
#15
Kapila Taneja, Bijender Kumar Bajaj, Sandeep Kumar, Neeraj Dilbaghi
Intravascular thrombosis is one of the major causes of variety of cardiovascular disorders leading to high mortality worldwide. Fibrinolytic enzymes from microbial sources possess ability to dissolve these clots and help to circumvent these problems in more efficient and safer way. In the present study, fibrinolytic protease with higher fibrinolytic activity than plasmin was obtained from Serratia sp. KG-2-1 isolated from garbage dump soil. Response surface methodology was used to study the interactive effect of concentration of maltose, yeast extract + peptone (1:1), incubation time, and pH on enzyme production and biomass...
July 2017: 3 Biotech
https://www.readbyqxmd.com/read/28656379/physiology-and-pathophysiology-of-the-plasminogen-system-in-the-kidney
#16
REVIEW
Per Svenningsen, Gitte Rye Hinrichs, Rikke Zachar, Rikke Ydegaard, Boye L Jensen
The plasminogen system is important for fibrinolysis in addition to tissue remodeling and inflammation with significance for kidney disease. The system consists of the circulating zymogen plasminogen (Plg) and the tissue- and urokinase-type plasminogen activators, tPA and uPA, expressed in the glomeruli, endothelium and tubular epithelium, respectively, and the inhibitors α2-antiplasmin and plasminogen activator inhibitor-type1, PAI-1. Plasminogen is activated by surface receptors, some with renal expression: urokinase-type plasminogen activator receptor (uPAR), plasminogen receptor KT (Plg-RKT), and tPA, most evident in the endothelium...
June 27, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28653850/discovery-and-evaluation-of-anti-fibrinolytic-plasmin-inhibitors-derived-from-5-4-piperidyl-isoxazol-3-ol-4-piol
#17
Thomas C Schmidt, Per-Olof Eriksson, David Gustafsson, David Cosgrove, Bente Frølund, Jonas Boström
Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known drug and lysine analogue tranexamic acid. Guided by shape similarities toward a previously discovered lead compound, 5-(4-piperidyl)isoxazol-3-ol, a set of 16 structurally similar compounds was assembled and investigated. Successfully, in vitro measurements revealed one compound, 5-(4-piperidyl)isothiazol-3-ol, superior in potency compared to the initial lead...
July 12, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28648598/myelin-basic-protein-stimulates-plasminogen-activation-via-tissue-plasminogen-activator-following-binding-to-independent-l-lysine-containing-domains
#18
Mario Gonzalez-Gronow, Jenny L Fiedler, Cristian Farias Gomez, Fang Wang, Rupa Ray, Paul D Ferrell, Salvatore V Pizzo
Myelin basic protein (MBP) is a key component of myelin, the specialized lipid membrane that encases the axons of all neurons. Both plasminogen (Pg) and tissue-type plasminogen activator (t-PA) bind to MBP with high affinity. We investigated the kinetics and mechanisms involved in this process using immobilized MBP and found that Pg activation by t-PA is significantly stimulated by MBP. This mechanism involves the binding of t-PA via a lysine-dependent mechanism to the Lys(91) residue of the MBP NH2-terminal region Asp(82) -Pro(99), and the binding of Pg via a lysine-dependent mechanism to the Lys(122) residue of the MBP COOH-terminal region Leu(109)-Gly(126)...
June 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28633085/biotechnological-production-of-recombinant-tissue-plasminogen-activator-protein-reteplase-from-transplastomic-tobacco-cell-cultures
#19
Diego Hidalgo, Maryam Abdoli-Nasab, Mokhtar Jalali-Javaran, Roque Bru-Martínez, Rosa M Cusidó, Purificación Corchete, Javier Palazon
Transplastomic plants are a system of choice for the mass production of biopharmaceuticals due to the polyploidy of the plastid genome and the low risk of pollen-mediated outcrossing because of maternal inheritance. However, as field-grown plants, they can suffer contamination by agrochemicals and fertilizers, as well as fluctuations in yield due to climatic changes and infections. Tissue-type plasminogen activator (tPA), a protein used to treat heart attacks, converts plasminogen into plasmine, which digests fibrin and induces the dissolution of fibrin clots...
June 13, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28630480/pro-invasive-stimuli-and-the-interacting-protein-hsp70-favour-the-route-of-alpha-enolase-to-the-cell-surface
#20
Giovanni Perconti, Cristina Maranto, Daniele P Romancino, Patrizia Rubino, Salvatore Feo, Antonella Bongiovanni, Agata Giallongo
Cell surface expression of alpha-enolase, a glycolytic enzyme displaying moonlighting activities, has been shown to contribute to the motility and invasiveness of cancer cells through the protein non-enzymatic function of binding plasminogen and enhancing plasmin formation. Although a few recent records indicate the involvement of protein partners in the localization of alpha-enolase to the plasma membrane, the cellular mechanisms underlying surface exposure remain largely elusive. Searching for novel interactors and signalling pathways, we used low-metastatic breast cancer cells, a doxorubicin-resistant counterpart and a non-tumourigenic mammary epithelial cell line...
June 19, 2017: Scientific Reports
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