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https://www.readbyqxmd.com/read/28079982/recombinant-soluble-apyrase-apt102-inhibits-thrombosis-and-intimal-hyperplasia-in-vein-grafts-without-adversely-affecting-hemostasis-or-re-endothelialization
#1
Y Ji, O Adeola, T L Strawn, S S Jeong, R Chen, W P Fay
BACKGROUND: Occlusion of vein grafts (VGs) after bypass surgery due to thrombosis and intimal hyperplasia (IH) is a major clinical problem. Apyrases are enzymes that scavenge extracellular ATP and ADP and promote adenosine formation at sites of vascular injury and hence have potential to inhibit vein graft pathology. OBJECTIVES: We examined the effects of recombinant soluble human apyrase, APT102, on platelets, smooth muscle cells (SMCs), and endothelial cells (ECs) in vitro and thrombosis and IH in murine VGs...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079976/maresin-1-induces-a-novel-pro-resolving-phenotype-in-human-platelets
#2
Katie L Lannan, Sherry L Spinelli, Neil Blumberg, Richard P Phipps
BACKGROUND: Antiplatelet therapy is a cornerstone of modern medical practice and is routinely employed to reduce the likelihood of myocardial infarction, thrombosis, and stroke. However, current antiplatelet therapies, such as aspirin, often have adverse side effects, including increased risk of bleeding, and some patients are relatively "aspirin-resistant". Platelets are intimately involved in hemostasis and inflammation, and clinical consequences are associated with excessive or insufficient platelet activation...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28078811/the-effects-of-nanomaterials-on-blood-coagulation-in-hemostasis-and-thrombosis
#3
REVIEW
Jan Simak, Silvia De Paoli
The blood coagulation balance in the organism is achieved by the interaction of the blood platelets (PLTs) with the plasma coagulation system (PCS) and the vascular endothelial cells. In healthy organism, these systems prevent thrombosis and, in events of vascular damage, enable blood clotting to stop bleeding. The dysregulation of hemostasis may cause serious thrombotic and/or hemorrhagic pathologies. Numerous engineered nanomaterials are being investigated for biomedical purposes and are unavoidably exposed to the blood...
January 11, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28069828/lpa1-receptor-mediated-thromboxane-a2-release-is-responsible-for-lysophosphatidic-acid-induced-vascular-smooth-muscle-contraction
#4
Péter Tibor Dancs, Éva Ruisanchez, Andrea Balogh, Cecília Rita Panta, Zsuzsanna Miklós, Rolf M Nüsing, Junken Aoki, Jerold Chun, Stefan Offermanns, Gábor Tigyi, Zoltán Benyó
Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6 In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA1-3 agonist VPC31143 induced dose-dependent vasoconstriction...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28065857/downstream-regulatory-element-antagonist-modulator-a-target-for-anti-thrombotic-agents
#5
Jaehyung Cho
Circulating platelets participate in the process of numerous diseases including thrombosis, inflammation, and cancer. Thus, it is of great importance to understand the underlying mechanisms mediating platelet activation under disease conditions. Emerging evidence indicates that despite the lack of a nucleus, platelets possess molecules that are involved in gene transcription in nucleated cells. This review will summarize downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, and highlight recent findings suggesting its novel non-transcriptional role in hemostasis and thrombosis...
January 5, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28034889/alteration-of-blood-clotting-and-lung-damage-by-protamine-are-avoided-using-the-heparin-and-polyphosphate-inhibitor-uhra
#6
Manu Thomas Kalathottukaren, Libin Abraham, Piyushkumar R Kapopara, Benjamin F L Lai, Rajesh A Shenoi, Federico I Rosell, Edward M Conway, Edward L G Pryzdial, James H Morrissey, Charles A Haynes, Jayachandran N Kizhakkedathu
Anticoagulant therapy associated bleeding and pathological thrombosis, pose serious risks to hospitalized patients. Both complications could be mitigated by developing new therapeutics that safely neutralize anticoagulant activity and inhibit activators of the intrinsic blood clotting pathway, such as polyphosphate (polyP) and extracellular nucleic acids. The latter strategy could reduce the use of anticoagulants, potentially decreasing bleeding events. However, previously described cationic inhibitors of polyP and extracellular nucleic acids, exhibit both non-specific binding and adverse effects on blood clotting that limit their use...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/28031960/the-melding-of-nanomedicine-in-thrombosis-imaging-and-treatment-a-review
#7
REVIEW
Varvara Karagkiozaki, Foteini Pappa, Despoina Arvaniti, Anestis Moumkas, Dimitrios Konstantinou, Stergios Logothetidis
Thromboembolic diseases constitute a plague in our century, wherein an imbalance of hemostasis leads to thrombus formation and vessels constriction reducing blood flow. Hence, the recent rise of nanomedicine gives birth to advanced diagnostic modalities and therapeutic agents for the early diagnosis and treatment of such diseases. Multimodal nanoagents for the detection of intravascular thrombi and nanovehicles for thrombus-targeted fibrinolytic therapy are few paradigms of nanomedicine approaches to overcome current diagnostic treatment roadblocks and persistent clinical needs...
June 2016: Future Science OA
https://www.readbyqxmd.com/read/28028021/ask1-regulates-platelet-granule-secretion-thromboxane-a2-generation-and-thrombus-formation-in-mice
#8
Meghna U Naik, Pravin Patel, Randall Derstine, Ramya Turaga, Xi Chen, Kalyan Golla, Keith B Neeves, Hidenori Ichijo, Ulhas P Naik
Mitogen activated protein kinases (MAPKs) are expressed in platelets and are activated downstream of physiological agonists. Pharmacological and genetic evidence indicate that MAPKs play a significant role in hemostasis and thrombosis, but it is not well understood how MAPKs are activated upon platelet stimulation. Here, we show that Apoptosis Signal-regulating Kinase 1 (ASK1), a member of the MAP3K family, is expressed in both human and murine platelets. ASK1 is rapidly and robustly activated upon platelet stimulation by physiological agonists...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/28017497/developmental-hemostasis-a-lifespan-from-neonates-and-pregnancy-to-the-young-and-elderly-adult-in-a-european-white-population
#9
Ulrike Nowak-Göttl, Verena Limperger, Gili Kenet, Frauke Degenhardt, Roman Arlt, Justus Domschikowski, Hartmut Clausnizer, Jürgen Liebsch, Ralf Junker, Dagmar Steppat
Absolute values of reference ranges for coagulation assays in humans vary within the entire lifespan and confirm the concept of developmental hemostasis. It is known that physiologic concentrations of coagulation factors (F) gradually increase over age: they are lower in premature infants as compared to full-term babies, healthy children or adults. Here we demonstrate in a cohort of 1011 blood donors and in a group of 193 healthy pregnant women, that the process of developmental hemostasis proceeds in adults...
December 5, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28007958/polyphosphate-and-rna-differentially-modulate-the-contact-pathway-of-blood-clotting
#10
Joshua M Gajsiewicz, Stephanie A Smith, James H Morrissey
The contact pathway of the plasma clotting cascade is dispensable for normal hemostasis, but contributes to thrombosis and serves as a bridge between inflammation and coagulation. This pathway is triggered upon exposure of plasma to certain anionic polymers and artificial surfaces. Recently, extracellular nucleic acids and inorganic polyphosphate (polyP) have been implicated as being important (patho)physiologically relevant activators of this pathway. However, mechanistic details regarding how nucleic acids or polyP modulate the individual reactions of the contact pathway have been lacking...
December 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27943214/isolation-of-platelet-derived-extracellular-vesicles
#11
Maria Aatonen, Sami Valkonen, Anita Böing, Yuana Yuana, Rienk Nieuwland, Pia Siljander
Platelets participate in several physiological functions, including hemostasis, immunity, and development. Additionally, platelets play key roles in arterial thrombosis and cancer progression. Given this plethora of functions, there is a strong interest of the role of platelet-derived (extracellular) vesicles (PDEVs) as functional mediators and biomarkers. Moreover, the majority of the blood-borne EVs are thought to originate from either platelets or directly from the platelet precursor cells, the megakaryocytes, which reside in the bone marrow...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27941211/-immunity-and-cancer-associated-thrombosis
#12
Andrzej Majdan, Aleksandra Majdan, Patrycja Ziober-Malinowska
In cancer patients, thrombosis is commonly found complication. There are many established risk factors which may be responsible for thrombosis in this group of patients. Especially the factors connected with treatment and the cancer itself, seem to be significant in the pathogenesis of thromboembolism. On the other hand, the reactions between cancer, hemostasis and immunological system seem to be important in initiation of the thrombotic process. In this review, on the basis of current literature, we have analyzed the relationship between neoplasmatic thrombosis and immunological disorders...
2016: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/27935296/graphene-montmorillonite-composite-sponge-for-safe-and-effective-hemostasis
#13
Guofeng Li, Kecheng Quan, Yuping Liang, Tianyi Li, Qipeng Yuan, Lei Tao, Qian Xie, Xing Wang
Montmorillonite (MMT) is considered to be the most effective hemostat among natural phyllosilicates. However, there is a barrier against using MMT for the commercial hemostatics because the invaded MMT powders might cause thrombosis in vessel. Until now, it is still a challenge to manage the release of MMT and eliminate its side effect. Herein, we present a graphene-MMT composite sponge (GMCS), synthesized under a hydrothermal reaction, fixing MMT powders into the cross-linked graphene sheets. We demonstrate that only a few embedded MMT can evoke remarkable platelet stimulation at the sponge interface, while maintaining fast plasma absorbency of the innate sponge...
December 28, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27932349/nadph-oxidase-2-and-atherothrombosis-insight-from-chronic-granulomatous-disease
#14
REVIEW
Francesco Violi, Roberto Carnevale, Lorenzo Loffredo, Pasquale Pignatelli, John I Gallin
The phagocytic cell enzyme NADPH oxidase-2 (Nox2) is critical for killing micro-organisms via production of reactive oxygen species and thus is a key element of the innate immune system. Nox2 is also detectable in endothelial cells and platelets where it has vasoconstrictive and aggregating properties, respectively. Patients with X-linked chronic granulomatous disease with hereditary Nox2 deficiency not only have impaired bacterial killing but, in association with loss of Nox2 function, also have enhanced carotid artery dilation, impaired platelet-related thrombosis, and reduced carotid atherosclerotic burden...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27917714/antiplatelet-and-anticoagulation-treatment-in-patients-with-thrombocytopenia
#15
Nuccia Morici, Silvia Cantoni, Paola Vallerio, Marco Cattaneo, Stefano Savonitto
Thrombocytopenia (TP) is a common finding in patients hospitalized for cardiovascular causes and needing antiplatelet and anticoagulant therapies. However, TP is not only a numeric parameter, but mostly a dynamic condition affected by the patients' underlying disorders and concomitant treatments. Platelets are important players in the hemostatic process, taking part to both primary and secondary hemostasis. Although both TP and antithrombotic treatment contribute to the risk of bleeding, the complexity of the pathogenesis of bleeding events makes it difficult to predict them accurately simply based on these two parameters...
December 5, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27913536/reversal-of-direct-oral-anticoagulants-a-practical-approach
#16
Andrew W Shih, Mark A Crowther
Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
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
#17
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/27886814/regulation-of-platelet-activation-and-coagulation-and-its-role-in-vascular-injury-and-arterial-thrombosis
#18
REVIEW
Maurizio Tomaiuolo, Lawrence F Brass, Timothy J Stalker
Hemostasis requires tightly regulated interaction of the coagulation system, platelets, blood cells, and vessel wall components at a site of vascular injury. Dysregulation of this response may result in excessive bleeding if the response is impaired, and pathologic thrombosis with vessel occlusion and tissue ischemia if the response is robust. Studies have elucidated the major molecular signaling pathways responsible for platelet activation and aggregation. Antithrombotic agents targeting these pathways are in clinical use...
January 2017: Interventional cardiology clinics
https://www.readbyqxmd.com/read/27876598/antithrombotic-activity-of-batroxase-a-metalloprotease-from-bothrops-atrox-venom-in-a-model-of-venous-thrombosis
#19
Anna L Jacob-Ferreira, Danilo L Menaldo, Marco A Sartim, Thalita B Riul, Marcelo Dias-Baruffi, Suely V Sampaio
BACKGROUND: Snake venoms are great sources of bioactive molecules, which may be used as models for new drugs. Toxins that interfere in hemostasis have received considerable attention over the years. OBJECTIVES: This study aimed at the evaluation of the antithrombotic activity of Batroxase, a P-I metalloprotease from Bothrops atrox venom, in an animal model of venous thrombosis. METHODS: The antithrombotic activity of Batroxase was tested in vivo in a model based on two factors of the Virchow's Triad: blood flow alterations (partial stenosis of the inferior vena cava), and vessel wall injury (10% ferric chloride for 5min), in comparison with sodium heparin (positive control) and saline (negative control)...
February 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27876233/role-of-platelets-in-neutrophil-extracellular-trap-net-production-and-tissue-injury
#20
REVIEW
Seok-Joo Kim, Craig N Jenne
In addition to their well-known role as the cellular mediator of thrombosis, numerous studies have identified key roles for platelets during various disease processes. Importantly, platelets play a critical role in the host immune response, directly interacting with, and eliminating pathogens, from the blood stream. In addition to pathogen clearance, platelets also contribute to leukocyte recruitment at sites of infection and inflammation, and modulate leukocyte activity. Platelet interaction with activated neutrophils is a potent inducer of neutrophil extracellular trap (NET)...
December 2016: Seminars in Immunology
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