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Platelet Aggregation

Katharina Grundler, Raffaela Rotter, Sloane Tilley, Joachim Pircher, Thomas Czermak, Mustaf Yakac, Erik Gaitzsch, Steffen Massberg, Florian Krötz, Hae-Young Sohn, Ulrich Pohl, Hanna Mannell, Bjoern F Kraemer
INTRODUCTION: Platelets possess critical hemostatic functions in the system of thrombosis and hemostasis, which can be affected by a multitude of external factors. Previous research has shown that platelets have the capacity to synthesize proteins de novo and more recently a multicatalytic protein complex, the proteasome, has been discovered in platelets. Due to its vital function for cellular integrity, the proteasome has become a therapeutic target for anti-proliferative drug therapies in cancer...
October 13, 2016: Thrombosis Research
Naoaki Morihara, Atsuko Hino
Aged garlic extract (AGE), a garlic preparation rich in water-soluble cysteinyl moieties, has been reported to have multiple beneficial effects on cardiovascular disease including inhibition of platelet aggregation. However, the mode of AGE action on platelets has not been clear. In this study, we examined the effect of AGE on the functional property of platelet by administering AGE to rats and evaluating the platelet aggregation in response to collagen in vitro. We found that AGE treatment significantly reduced the ability of platelet to aggregate and this effect of AGE was manifested on the 14 day, but not 7 day of treatment...
October 20, 2016: Journal of Natural Medicines
Janina Jamasbi, Remco T A Megens, Mariaelvy Bianchini, Kerstin Uhland, Götz Münch, Martin Ungerer, Shachar Sherman, Alexander Faussner, Richard Brandl, Christine John, Johannes Buchner, Christian Weber, Reinhard Lorenz, Natalie Elia, Wolfgang Siess
To enhance the antithrombotic properties of recombinant glycoprotein VI fragment crystallizable (GPVI-Fc), the authors incubated GPVI-Fc with anti-human Fc antibodies to cross-link the Fc tails of GPVI-Fc. Cross-linking potentiated the inhibition of human plaque- and collagen-induced platelet aggregation by GPVI-Fc under static and flow conditions without increasing bleeding time in vitro. Cross-linking with anti-human-Fc Fab2 was even superior to anti-human-Fc immunoglobulin G (IgG). Advanced optical imaging revealed a continuous sheath-like coverage of collagen fibers by cross-linked GPVI-Fc complexes...
April 2016: JACC. Basic to Translational Science
Ren-Chieh Wu, Ping-Tse Chou, Li-Kuang Chen
BACKGROUND: Thrombosis and coagulopathy are the commonest hematological manifestations of envenomation of Russell's viper venom (RVV). Factor X is activated by a factor X-activating enzyme from Russell's viper venom (RVV-X) to start the coagulation cascade. We established an animal model with local ischemic effects induced by RVV. We tried to treat RVV envenomation with antiplatelets and anticoagulants without recourse to antivenom. METHODS: RVV was injected into the foot pad of mice...
2016: Thrombosis Journal
Xiaohong Ruby Xu, Naadiya Carrim, Miguel Antonio Dias Neves, Thomas McKeown, Tyler W Stratton, Rodrigo Matos Pinto Coelho, Xi Lei, Pingguo Chen, Jianhua Xu, Xiangrong Dai, Benjamin Xiaoyi Li, Heyu Ni
Platelets are central mediators of thrombosis and hemostasis. At the site of vascular injury, platelet accumulation (i.e. adhesion and aggregation) constitutes the first wave of hemostasis. Blood coagulation, initiated by the coagulation cascades, is the second wave of thrombin generation and enhance phosphatidylserine exposure, can markedly potentiate cell-based thrombin generation and enhance blood coagulation. Recently, deposition of plasma fibronectin and other proteins onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that occurs prior to platelet accumulation (i...
2016: Thrombosis Journal
Hui-Ju Tsai, Ching-Ping Tseng
Multiple functions of platelets in various physiological and pathological conditions have prompted considerable attention on understanding how platelets are generated and activated. Of the adaptor proteins that are expressed in megakaryocytes and platelets, Disabled-2 (Dab2) has been demonstrated in the past decades as a key regulator of platelet signaling. Dab2 has two alternative splicing isoforms p82 and p59. However, the mode of Dab2's action remains to be clearly defined. In this review, we highlight the current understanding of Dab2 expression and function in megakaryocytic differentiation, platelet activation and integrin signaling...
2016: Thrombosis Journal
Yuhang Zhou, Shaji Abraham, Stephanie Renna, Leonard C Edelstein, Carol A Dangelmaier, Alexander Y Tsygankov, Satya P Kunapuli, Paul F Bray, Steven E McKenzie
OBJECTIVE: The objective of this study is to investigate the role of T-cell ubiquitin ligand-2 (TULA-2) in the platelet Fc receptor for IgG IIA (FcγRIIA) pathway and in the pathogenesis of heparin-induced thrombocytopenia (HIT). APPROACH AND RESULTS: HIT is a life-threatening thrombotic disease in which IgG antibodies against the heparin-platelet factor 4 complex activate platelets via FcγRIIA. We reported previously differential expression of TULA-2 in human population was linked to FcγRIIA responsiveness...
October 20, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Rick Morrison, Zhaohua Zheng, Ian G Jennings, Philip E Thompson, Jasim M A Al-Rawi
To continue our study of 2-morpholino-benzoxazine based compounds, which show useful activity against PI3K family enzymes or antiplatelet activity, we designed and synthesized a series of linear 6.7-fused, 5,6-angular fused and 7,8-angular fused-aryl-morpholino-naphth-oxazines. The compounds were prepared from substituted 2-hydroxynaphthoic acid to give the corresponding thioxo analogues 8, 9, 15 and 19. The thioxo products were then converted to the morpholino substituted analogue. The aryl group was introduced by Suzuki coupling of bromo precursors...
October 5, 2016: Bioorganic & Medicinal Chemistry Letters
Y Zaid, N Senhaji, Y Darif, K Kojok, M Oudghiri, A Naya
Platelet activation is a complex balance of positive and negative signaling pathways. Several protein kinase C (PKC) isoforms are expressed in human platelets. They are a major regulator of platelet granule secretion, activation and aggregation activity. One of those isoforms is the PKCδ isozyme, it has a central yet complex role in platelets such as opposite signaling functions depending on the nature of the agonist, it concentration and pathway. In fact, it has been shown that PKCδ has an overall negative influence on platelet function in response to collagen, while, following PAR stimulation, PKCδ has a positive effect on platelet function...
July 2016: Current Research in Translational Medicine
Jih-Jung Chen, Tung-Han Tsai, Hsiang-Ruei Liao, Li-Chai Chen, Yueh-Hsiung Kuo, Ping-Jyun Sung, Chun-Lin Chen, Chun-Sheng Wei
Two new sesquiterpenoids-13-hydroxycurzerenone (1) and 1-oxocurzerenone (2)-have been isolated from the rhizomes of Curcuma zedoaria, together with 13 known compounds (3-15). The structures of two new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 13-hydroxycurzerenone (1), 1-oxocurzerenone (2), curzerenone (3), germacrone (4), curcolone (5), procurcumenol (6), ermanin (7), curcumin (8), and a mixture of stigmast-4-en-3,6-dione (12) and stigmasta-4,22-dien-3,6-dione (13) exhibited inhibition (with inhibition % in the range of 21...
October 17, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sibel Hacioglu, Aysun Karabulut, Ismail Sari, Ali Keskin
The aim of this study was to determine the frequency of haemostatic abnormalities in women with menorrhagia and to evaluate their effect on quality of life (QoL). The study population was composed of patients with menorrhagia seen in the outpatient clinic, having a score of >185 with a pictorial blood assessment chart. Structured questionnaires were used in the assessment of demographic characteristics and QoL, and patients were tested for bleeding disorders. Ninety women were recruited for the study. Bleeding disorders were detected in 40% of them: 11...
October 20, 2016: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
Julia Riedl, Alexandra Kaider, Christine Marosi, Gerald W Prager, Beate Eichelberger, Alice Assinger, Ingrid Pabinger, Simon Panzer, Cihan Ay
Platelets are suggested to play a crucial role in cancer progression and the prothrombotic state of cancer patients. Here, we aimed to examine the activation status of platelets in cancer patients and investigate their association with risk of death and occurrence of venous thromboembolism (VTE) in a prospective observational cohort study. We measured platelet surface P-selectin, activated glycoprotein (GP) IIb/IIIa and monocyte-platelet aggregate (MPA) formation in vivo and platelet response to ex vivo stimulation with agonists of protease-activated receptor (PAR) -1, -4, and GPVI, by whole blood flow cytometry, before beginning of chemotherapy and repeatedly during the first six months thereafter (total number of samples analysed: 230)...
October 20, 2016: Thrombosis and Haemostasis
Anna Ågren, Margareta Holmström, David E Schmidt, Kazuya Hosokawa, Margareta Blombäck, Paul Hjemdahl
Patients with type 3 von Willebrand disease (VWD-3) have no measurable levels of VW factor (VWF) and usually require treatment with VWF-FVIII concentrate to prevent and/or stop bleeding. Even though the patients are treated prophylactically, they may experience bleeding symptoms. The aim of this study was to evaluate the effect of VWF-FVIII concentrate treatment in VWD-3 patients with the Total Thrombus Analysis System (T-TAS(®)), which measures thrombus formation under flow conditions. Coagulation profiles of 10 VWD-3 patients were analysed using T-TAS before and 30 minutes after VWF-FVIII concentrate (Haemate(®)) injection...
October 20, 2016: Thrombosis and Haemostasis
Mojtaba Shafiekhani, Pouya Faridi, Javad Kojuri, Soha Namazi
OBJECTIVE: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. MATERIALS AND METHODS: This randomized controlled clinical trial (RCT) was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA) induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l), epinephrine (20 μmol/l), collagen(0...
September 2016: Avicenna Journal of Phytomedicine
Raphael Leblanc, Olivier Peyruchaud
Blood platelets have been known for more than a century as important partners for successful metastatic dissemination of solid tumors. Cancer cell-induced platelet activation is a key event responsible for prometastatic activity of platelets. Blocking platelet aggregation inhibits the progression of skeletal metastases through mechanisms that are not fully understood. The establishment and progression of bone metastases are strongly influenced by the bone remodeling process. Growth factors and cytokines released upon platelet activation may contribute to both skeletal tumor growth and osteolytic lesions...
September 2016: Journal of Bone Oncology
Laura Acquasaliente, Daniele Peterle, Simone Tescari, Nicola Pozzi, Vittorio Pengo, Vincenzo De Filippis
: β2-Glycoprotein I (β2GpI) is the major autoantigen in the antiphospholipid syndrome, a thrombotic autoimmune disease. Nonetheless, the physiological role of β2GpI is still unclear. In a recent work, we have shown that β2GpI selectively inhibits the procoagulant functions of human a-thrombin (αT) (i.e. prolongs fibrin clotting time, tc, and inhibits αT-induced platelets aggregation) without affecting the unique anticoagulant activity of the protease, i.e. the proteolytic generation of the anticoagulant protein C (PC) from the PC zymogen, which interacts with αT exclusively at the protease catalytic site...
October 19, 2016: Biochemical Journal
Joan Raouf, Fariborz Mobarrez, Karin Larsson, Per-Johan Jakobsson, Marina Korotkova
Microsomal prostaglandin E2 synthase-1 (mPGES-1) constitutes an essential player of inflammation and is involved in the pathogenesis of rheumatoid arthritis (RA). Platelets participate in the regulation of inflammatory processes by the release of pro-inflammatory mediators and platelet-derived microparticles (PMPs). However, the role of the inducible mPGES-1/PGE2 pathway on platelet functions has not been investigated. Here we report a significant impact of mPGES-1 on platelet functions during inflammation...
October 7, 2016: Clinical Science (1979-)
Kyungho Kim, Jing Li, Andrew Barazia, Alan Tseng, Seock-Won Youn, Giovanni Abbadessa, Yi Yu, Brian Schwartz, Robert K Andrews, Victor R Gordeuk, Jaehyung Cho
Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target for thromboinflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in Phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50-500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets...
October 6, 2016: Haematologica
Leonardo A Moraes, Amanda J Unsworth, Sakthivel Vaiyapuri, Marfoua S Ali, Parvathy Sasikumar, Tanya Sage, Gagan D Flora, Alex P Bye, Neline Kriek, Emilie Dorchies, Olivier Molendi-Coste, David Dombrowicz, Bart Staels, David Bishop-Bailey, Jonathan M Gibbins
OBJECTIVE: Although initially seemingly paradoxical because of the lack of nucleus, platelets possess many transcription factors that regulate their function through DNA-independent mechanisms. These include the farnesoid X receptor (FXR), a member of the superfamily of ligand-activated transcription factors, that has been identified as a bile acid receptor. In this study, we show that FXR is present in human platelets and FXR ligands, GW4064 and 6α-ethyl-chenodeoxycholic acid, modulate platelet activation nongenomically...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Giovanni Cimmino, Francesco S Loffredo, Alberto Morello, Saverio D Elia, Raffaele De Palma, Plinio Cirillo, Paolo Golino
In the last twenty years, our comprehension of the molecular mechanisms involved in formation, progression and complication of atherosclerotic plaque has advanced significantly and the main role of inflammation and immunity in this phenomenon is now largely accepted. Accumulating evidence highlight the crucial role of different inflammatory and immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerotic lesion, particularly in contributing to its complications, such as rupture or ulceration...
October 13, 2016: Current Cardiology Reviews
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