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https://www.readbyqxmd.com/read/27927771/propagation-of-thrombosis-by-neutrophils-and-extracellular-nucleosome-networks
#1
Susanne Pfeiler, Konstantin Stark, Steffen Massberg, Bernd Engelmann
Neutrophils, early mediators of innate immune defense, are recruited to developing thrombi in different types of thrombosis. They amplify intravascular coagulation by stimulating the tissue factor-dependent extrinsic pathway via inactivation of endogenous anticoagulants, enhancing factor XII activation or decreasing plasmin generation. Neutrophil-dependent prothrombotic mechanisms are supported by the externalization of decondensed nucleosomes and granule proteins that together form neutrophil extracellular traps...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27923263/microparticles-and-fibrinolysis
#2
Loris Vallier, Sylvie Cointe, Romaric Lacroix, Amandine Bonifay, Coralie Judicone, Françoise Dignat-George, Hau C Kwaan
Microparticles (MPs) are submicronic vesicles which are formed by budding of the cellular membrane of virtually any cell type in response to cell activation or apoptosis. Both circulating MPs and MPs generated within tissues harbor molecules with a large repertoire of biological activities and transfer material to target cells. Depending on their cellular origin, the stimuli triggering their formation, or their localization, they may participate in the maintenance of organ or vascular homeostasis as well as inducing dysfunction...
December 6, 2016: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/27900590/assessment-of-oxidative-nitrative-modifications-of-plasma-proteins-selected-rotem-parameters-and-kinetics-of-fibrinogen-polymerization-in-patients-with-multiple-myeloma-at-diagnosis
#3
W Nowak, J Treliński, K Chojnowski, J Matczak, M Robak, M Misiewicz, P Nowak
Patients with multiple myeloma (MM) are at increased risk of thrombosis. Growing evidence indicates that oxidative and nitrative modifications of proteins, including fibrinogen, may lead to changes in hemostasis. The study compares samples from patients with MM at diagnosis and healthy volunteers with regard to the oxidative/nitrative modifications of proteins, ROTEM and thrombin-catalyzed fibrin polymerization. The content of carbonyl groups in plasma proteins of patients with MM was significantly higher than in controls (2...
January 2017: Medical Oncology
https://www.readbyqxmd.com/read/27898513/inhibition-of-plasmin-generation-in-plasma-by-heparin-low-molecular-weight-heparin-and-a-covalent-antithrombin-heparin-complex
#4
Gabriela M T Chang, Helen M Atkinson, Leslie R Berry, Anthony K C Chan
The clinical limitations of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) led to the development of an antithrombin-heparin covalent complex (ATH), which displays superior anticoagulant abilities compared with UFH. A recent study investigating its interaction with fibrinolysis showed that ATH inhibited free and fibrin bound plasmin and decreased plasmin generation on fibrin clots. These studies were conducted using purified components and did not elucidate the interaction of ATH with plasmin in the presence of its natural inhibitors α2-antiplasmin (α2-AP) and α2-macroglobulin (α2-M)...
November 24, 2016: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/27881952/tissue-type-plasminogen-activator-tpa-modulates-the-postsynaptic-response-of-cerebral-cortical-neurons-to-the-presynaptic-release-of-glutamate
#5
Valerie Jeanneret, Fang Wu, Paola Merino, Enrique Torre, Ariel Diaz, Lihong Cheng, Manuel Yepes
Tissue-type plasminogen activator (tPA) is a serine proteinase released by the presynaptic terminal of cerebral cortical neurons following membrane depolarization (Echeverry et al., 2010). Recent studies indicate that the release of tPA triggers the synaptic vesicle cycle and promotes the exocytosis (Wu et al., 2015) and endocytic retrieval (Yepes et al., 2016) of glutamate-containing synaptic vesicles. Here we used electron microscopy, proteomics, quantitative phosphoproteomics, biochemical analyses with extracts of the postsynaptic density (PSD), and an animal model of cerebral ischemia with mice overexpressing neuronal tPA to study whether the presynaptic release of tPA also has an effect on the postsynaptic terminal...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27856467/plasmin-a-driver-of-hemovascular-dysfunction
#6
Andrew P Cap
No abstract text is available yet for this article.
November 17, 2016: Blood
https://www.readbyqxmd.com/read/27845251/heparan-sulfate-heparin-glycosaminoglycan-binding-alters-inhibitory-profile-and-enhances-anticoagulant-function-of-conserved-amblyomma-americanum-tick-saliva-serpin-19
#7
Željko M Radulović, Albert Mulenga
Some serine protease inhibitor (serpin) regulators of essential life pathways bind glycosaminoglycans (GAGs) to enhance inhibitory functions and achieve physiologically relevant rates. This study demonstrates that highly conserved Amblyomma americanum tick saliva serpin 19 (AAS19), a broad-spectrum inhibitor of hemostasis and inflammation system proteases and anticoagulant, can bind heparan sulfate/heparin (HS)GAGs and that this interaction alters its function. Substrate hydrolysis and unpaired t-test analyses revealed that HSGAG binding caused rAAS19 inhibitory activity to: (i) significantly increase against blood clotting factors (f) IIa (thrombin) and fIXa, (ii) significantly reduce against fXa and fXIIa and (iii) moderate to no effect against trypsin, kallikrein, papain, and plasmin...
November 12, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27826093/cytokine-and-estrogen-stimulation-of-endothelial-cells-augment-activation-of-the-prekallikrein-high-molecular-weight-kininogen-complex-implications-for-hereditary-angioedema-hae
#8
Kusumam Joseph, Baby G Tholanikunnel, Allen P Kaplan
BACKGROUND: When the prekallikrein-high molecular weight kininogen complex is bound to endothelial cells, prekallikrein is stoichiometrically converted to kallikrein due to release of heat shock protein-90 (Hsp90). While bradykinin formation is typically initiated by factor XII autoactivation it is also possible to activate factor XII either by kallikrein, thus formed, or plasmin. RATIONALE: Since attacks of hereditary angioedema can be related to infection and/or exposure to estrogen, we questioned whether estrogen or cytokine stimulation of endothelial cells could augment release of Hsp90 and prekallikrein activation...
November 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27814935/diuretic-resistance
#9
Ewout J Hoorn, David H Ellison
Diuretic resistance is defined as a failure to achieve the therapeutically desired reduction in edema despite a full dose of diuretic. The causes of diuretic resistance include poor adherence to drug therapy or dietary sodium restriction, pharmacokinetic issues, and compensatory increases in sodium reabsorption in nephron sites that are not blocked by the diuretic. To illustrate the pathophysiology and management of diuretic resistance, we describe a patient with nephrotic syndrome. This patient presented with generalized pitting edema and weight gain despite the use of oral loop diuretics...
November 1, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/27814656/alpha-enolase-eno1-a-potential-target-in-novel-immunotherapies
#10
Paola Cappello, Moitza Principe, Sara Bulfamante, Francesco Novelli
Alpha-enolase (ENO1) is a metabolic enzyme involved in the synthesis of pyruvate. It also acts as a plasminogen receptor and mediates the activation of plasmin and extracellular matrix degradation. In tumor cells, ENO1 is up-regulated and supports the Warburg effect; it is expressed at the cell surface, where it promotes cancer invasion, and is subjected to a specific array of post-translational modifications, namely acetylation, methylation and phosphorylation. ENO1 overexpression and post-translational modifications could be of diagnostic and prognostic value in many cancer types...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27813674/induction-of-tissue-factor-pathway-inhibitor-2-by-hcg-regulates-periovulatory-gene-expression-and-plasmin-activity
#11
Muraly Puttabyatappa, Linah F Al-Alem, Farnosh Zakerkish, Katherine L Rosewell, Mats Brännström, Thomas E Curry
A key event during the process of ovulation is an increased proteolytic activity that aids in breakdown of the follicular wall to permit oocyte release. How the activity of these proteases is regulated is still not known. We hypothesize that Tissue Factor Pathway Inhibitor 2 (TFPI2), a matrix-associated Kunitz-type serine protease inhibitor, plays a role in regulating proteolytic activity during the periovulatory period as in other tissues. TFPI2 is secreted into the extracellular matrix (ECM) where it is postulated to regulate physiological ECM remodeling...
November 4, 2016: Endocrinology
https://www.readbyqxmd.com/read/27797450/s2-subsite-variations-between-human-and-mouse-enzymes-plasmin-factor-xia-kallikrein-elucidate-inhibition-differences-by-tfpi-2-domain1-wildtype-leu17arg-mutant-and-aprotinin
#12
K Vadivel, Y Kumar, G I Ogueli, S M Ponnuraj, P Wongkongkathep, J A Loo, M S Bajaj, S P Bajaj
BACKGROUND: Using TFPI-2 Kunitz domain1 (KD1), we obtained a bifunctional antifibrinolytic molecule (KD1L17R -KT ) with C-terminal lysine (kringle domain binding) and P2'-residue arginine (improved specificity towards plasmin). KD1L17R -KT strongly inhibited human plasmin (hPm), with no inhibition of human kallikrein (hKLK) or factor XIa (hXIa). Furthermore, KD1L17R -KT reduced blood loss comparable to aprotinin in a mouse liver-laceration model of organ hemorrhage. However, effectiveness of these antifibrinolytic agents in a model of hemorrhage mimicking extremity trauma and their inhibition efficiencies for mouse enzymes (mPm, mKLK or mXIa) remain to be determined...
October 31, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27793534/plasmin-human-administration-in-acute-middle-cerebral-artery-ischemic-stroke-phase-1-2a-open-label-dose-escalation-safety-study
#13
Peter J Mitchell, Bernard Yan, Miroslav Brozman, Marc Ribo, Victor Marder, Kecia L Courtney, Jeffrey L Saver
BACKGROUND: This phase 1/2a, open-label, multicenter, dose-escalation, safety study describes the first evaluation of plasmin as an intracranial thrombolytic treatment for acute ischemic stroke in the middle cerebral artery. The rationale for intrathrombus administration is that plasmin would bind fibrin inside the targeted clot, protecting it from circulating inhibitors. METHODS: Plasmin was given in escalating doses within 9 hours of stroke onset, and treatment efficacy was determined in 5 patient cohorts (N = 40): cohort 1 (20 mg, ...
October 25, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/27783862/adipose-tissue-derived-plasminogen-activator-inhibitor-1-function-and-regulation
#14
Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/27773435/a-serine-protease-inhibitor-attenuates-aldosterone-induced-kidney-injuries-via-the-suppression-of-plasmin-activity
#15
Yutaka Kakizoe, Yoshikazu Miyasato, Tomoaki Onoue, Terumasa Nakagawa, Manabu Hayata, Kohei Uchimura, Jun Morinaga, Teruhiko Mizumoto, Masataka Adachi, Taku Miyoshi, Yoshiki Sakai, Kimio Tomita, Masashi Mukoyama, Kenichiro Kitamura
Emerging evidence has suggested that aldosterone has direct deleterious effects on the kidney independently of its hemodynamic effects. However, the detailed mechanisms of these direct effects remain to be elucidated. We have previously reported that camostat mesilate (CM), a synthetic serine protease inhibitor, attenuated kidney injuries in Dahl salt-sensitive rats, remnant kidney rats, and unilateral ureteral obstruction rats, suggesting that some serine proteases would be involved in the pathogenesis of kidney injuries...
September 30, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27772757/recombinant-tissue-plasminogen-activator-enhances-microparticle-release-from-mouse-brain-derived-endothelial-cells-through-plasmin
#16
Marie Garraud, Kahina Khacef, Anne-Clémence Vion, Claire Leconte, Min Yin, Jean-Marie Renard, Catherine Marchand-Leroux, Chantal M Boulanger, Isabelle Margaill, Virginie Beray-Berthat
Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is currently the only approved pharmacological strategy for acute ischemic stroke. However, rt-PA exhibits vascular toxicity mainly due to endothelial damage. To investigate the mechanisms underlying rt-PA-induced endothelial alterations, we assessed the role of rt-PA in the generation of endothelial microparticles (EMPs), emerging biological markers and effectors of endothelial dysfunction. The mouse brain-derived endothelial cell line bEnd...
November 15, 2016: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/27761105/fibrinogen-alpha-c-chain-5-9%C3%A2-kda-fragment-fic5-9-a-biomarker-for-various-pathological-conditions-is-produced-in-post-blood-collection-by-fibrinolysis-and-coagulation-factors
#17
Wataru Kikuchi, Motoi Nishimura, Takahisa Kuga, Sachio Tsuchida, Tatsuya Saito, Mamoru Satoh, Kenta Noda, Yoshio Kodera, Takeshi Tomonaga, Fumio Nomura
BACKGROUND: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube...
2016: Clinical Proteomics
https://www.readbyqxmd.com/read/27755234/expression-of-tissue-factor-in-epithelial-ovarian-carcinoma-is-involved-in-the-development-of-venous-thromboembolism
#18
Manabu Sakurai, Koji Matsumoto, Masahiko Gosho, Akiko Sakata, Yoshihiko Hosokawa, Yuri Tenjimbayashi, Takashi Katoh, Ayumi Shikama, Haruna Komiya, Hiroo Michikami, Nobutaka Tasaka, Azusa Akiyama-Abe, Sari Nakao, Hiroyuki Ochi, Mamiko Onuki, Takeo Minaguchi, Hiroyuki Yoshikawa, Toyomi Satoh
OBJECTIVES: Our 2007 study of 32 patients with ovarian cancer reported the possible involvement of tissue factor (TF) in the development of venous thromboembolism (VTE) before treatment, especially in clear cell carcinoma (CCC). This follow-up study further investigated this possibility in a larger cohort. METHODS: We investigated the intensity of TF expression (ITFE) and other variables for associations with VTE using univariate and multivariate analyses in 128 patients with epithelial ovarian cancer initially treated between November 2004 and December 2010, none of whom had received neoadjuvant chemotherapy...
October 17, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27743595/relevance-of-the-plasminogen-system-in-physiology-pathology-and-regeneration-of-oral-tissues-from-the-perspective-of-dental-specialties
#19
Christian Wehner, Klara Janjić, Hermann Agis
Plasmin is a proteolytic enzyme that is crucial in fibrinolysis. In oral tissues, the plasminogen system plays an essential role in physiological and pathological processes, which in addition to fibrinolysis include degradation of extracellular matrix, inflammation, immune response, angiogenesis, tissue remodeling, cell migration, and wound healing. Oral tissues reveal a change in the plasminogen system during pathological processes such as periodontitis, peri-implantitis, or pulpitis, as well as in response to mechanical load...
October 5, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/27722710/bioprinted-thrombosis-on-a-chip
#20
Yu Shrike Zhang, Farideh Davoudi, Philipp Walch, Amir Manbachi, Xuan Luo, Valeria Dell'Erba, Amir K Miri, Hassan Albadawi, Andrea Arneri, Xiaoyun Li, Xiaoying Wang, Mehmet Remzi Dokmeci, Ali Khademhosseini, Rahmi Oklu
Pathologic thrombosis kills more people than cancer and trauma combined; it is associated with significant disability and morbidity, and represents a major healthcare burden. Despite advancements in medical therapies and imaging, there is often incomplete resolution of the thrombus. The residual thrombus can undergo fibrotic changes over time through infiltration of fibroblasts from the surrounding tissues and eventually transform into a permanent clot often associated with post-thrombotic syndrome. In order to understand the importance of cellular interactions and the impact of potential therapeutics to treat thrombosis, an in vitro platform using human cells and blood components would be beneficial...
October 18, 2016: Lab on a Chip
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