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Platelet integrin

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https://www.readbyqxmd.com/read/28314136/platelet-microparticle-inspired-clot-responsive-nanomedicine-for-targeted-fibrinolysis
#1
Christa L Pawlowski, Wei Li, Michael Sun, Kavya Ravichandran, DaShawn Hickman, Clarissa Kos, Gurbani Kaur, Anirban Sen Gupta
Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger...
March 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28278197/the-role-of-platelet-and-endothelial-garp-in-thrombosis-and-hemostasis
#2
Elien Vermeersch, Frederik Denorme, Wim Maes, Simon F De Meyer, Karen Vanhoorelbeke, Justin Edwards, Ethan M Shevach, Derya Unutmaz, Hodaka Fujii, Hans Deckmyn, Claudia Tersteeg
BACKGROUND: Glycoprotein-A Repetitions Predominant protein (GARP or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of GARP in zebrafish. OBJECTIVES: To evaluate the role of GARP in platelet physiology and in thrombus formation using platelet and endothelial conditional GARP knock out mice. METHODS: Platelet and endothelial specific GARP knockout mice were generated using the Cre-loxP recombination system...
2017: PloS One
https://www.readbyqxmd.com/read/28277676/mechanistic-basis-for-the-binding-of-rgd-and-agdv-peptides-to-the-platelet-integrin-%C3%AE-iib%C3%AE-3
#3
Olga Kononova, Rustem I Litvinov, Dmitry S Blokhin, Vladimir V Klochkov, John W Weisel, Joel S Bennett, Valeri Barsegov
Binding of soluble fibrinogen to the activated conformation of the integrin αIIbβ3 is required for platelet aggregation and is mediated exclusively by the C-terminal AGDV-containing dodecapeptide (γC-12) sequence of the fibrinogen γ chain. However, peptides containing the Arg-Gly-Asp (RGD) sequences located in two places in the fibrinogen Aα chain inhibit soluble fibrinogen binding to αIIbβ3 and make substantial contributions to αIIbβ3 binding when fibrinogen is immobilized and when it is converted to fibrin...
March 9, 2017: Biochemistry
https://www.readbyqxmd.com/read/28271416/bleeding-tendency-and-platelet-function-during-treatment-with-romiplostim-in-children-with-severe-immune-thrombocytopenic-purpura
#4
Elena V Suntsova, Irina M Demina, Anastasia A Ignatova, Nikolay M Ershov, Natalia M Trubina, Juliya Dobrynina, Irina V Serkova, Zhanna S Supik, Ekaterina V Orekhova, Lili A Hachatryan, Natalia N Kotskaya, Aleksey V Pshonkin, Aleksey A Maschan, Galina A Novichkova, Mikhail A Panteleev
It has been suggested that platelet function in chronic immune thrombocytopenic purpura (ITP) may be abnormal. Thrombopoietin mimetics used for treatment can affect it, but the data remain limited. We investigated platelet function of 20 children diagnosed with severe ITP (aged 1-16 years, 12 females and eight males). Platelet functional activity in whole blood was characterized by flow cytometry before and after stimulation with SFLLRN plus collagen-related peptide. Levels of CD42b, PAC1, and CD62P, but not CD61 or annexin V, were significantly increased (P < 0...
March 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28254816/rxr-ligands-negatively-regulate-thrombosis-and-hemostasis
#5
Amanda J Unsworth, Gagan D Flora, Parvathy Sasikumar, Alexander P Bye, Tanya Sage, Neline Kriek, Marilena Crescente, Jonathan M Gibbins
OBJECTIVE: Platelets have been found to express intracellular nuclear receptors including the retinoid X receptors (RXRα and RXRβ). Treatment of platelets with ligands of RXR has been shown to inhibit platelet responses to ADP and thromboxane A2; however, the effects on responses to other platelet agonists and the underlying mechanism have not been fully characterized. APPROACH AND RESULTS: The effect of 9-cis-retinoic acid, docosahexaenoic acid and synthetic ligand for RXR, methoprene acid on collagen receptor (GPVI) agonists and thrombin-stimulated platelet function; including aggregation, granule secretion, integrin activation, calcium mobilization, integrin αIIbβ3 outside-in signaling and thrombus formation in vitro and in vivo were determined...
March 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28253287/platelet-gpiib-supports-initial-pulmonary-retention-but-inhibits-subsequent-proliferation-of-melanoma-cells-during-hematogenic-metastasis
#6
Katrin Echtler, Ildiko Konrad, Michael Lorenz, Simon Schneider, Sebastian Hofmaier, Florian Plenagl, Konstantin Stark, Thomas Czermak, Anca Tirniceriu, Martin Eichhorn, Axel Walch, Georg Enders, Steffen Massberg, Christian Schulz
Platelets modulate the process of cancer metastasis. However, current knowledge on the direct interaction of platelets and tumor cells is mostly based on findings obtained in vitro. We addressed the role of the platelet fibrinogen receptor glycoprotein IIb (integrin αIIb) for experimental melanoma metastasis in vivo. Highly metastatic B16-D5 melanoma cells were injected intravenously into GPIIb-deficient (GPIIb-/-) or wildtype (WT) mice. Acute accumulation of tumor cells in the pulmonary vasculature was assessed in real-time by confocal videofluorescence microscopy...
2017: PloS One
https://www.readbyqxmd.com/read/28252668/aggretin-venom-polypeptide-as-a-novel-anti-angiogenesis-agent-by-targeting-integrin-alpha2beta1
#7
Ching Hu Chung, Chien Hsin Chang, Chun Chieh Hsu, Kung Tin Lin, Hui Chin Peng, Tur Fu Huang
VEGF and VEGFR antibodies have been used as a therapeutic strategy to inhibit angiogenesis in many diseases; however, frequent and repeated administration of these antibodies to patients induces immunogenicity. In previous studies, we demonstrated that aggretin, a heterodimeric snake venom C-type lectin, exhibits pro-angiogenic activities via integrin α2β1 ligation. We hypothesised that small-mass aggretin fragments may bind integrin α2β1 and act as antagonists of angiogenesis. In this study, the anti-angiogenic efficacy of a synthesised aggretin α-chain C-terminus (AACT, residue 106-136) was evaluated in both in vitro and in vivo angiogenesis models...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28246700/integrin-signaling-in-atherosclerosis
#8
REVIEW
Alexandra C Finney, Karen Y Stokes, Christopher B Pattillo, A Wayne Orr
Atherosclerosis, a chronic lipid-driven inflammatory disease affecting large arteries, represents the primary cause of cardiovascular disease in the world. The local remodeling of the vessel intima during atherosclerosis involves the modulation of vascular cell phenotype, alteration of cell migration and proliferation, and propagation of local extracellular matrix remodeling. All of these responses represent targets of the integrin family of cell adhesion receptors. As such, alterations in integrin signaling affect multiple aspects of atherosclerosis, from the earliest induction of inflammation to the development of advanced fibrotic plaques...
February 28, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28218242/protein-disulfide-isomerase-secretion-following-vascular-injury-initiates-a-regulatory-pathway-for-thrombus-formation
#9
Sheryl R Bowley, Chao Fang, Glenn Merrill-Skoloff, Barbara C Furie, Bruce Furie
Protein disulfide isomerase (PDI), secreted by platelets and endothelial cells on vascular injury, is required for thrombus formation. Using PDI variants that form mixed disulfide complexes with their substrates, we identify by kinetic trapping multiple substrate proteins, including vitronectin. Plasma vitronectin does not bind to αvβ3 or αIIbβ3 integrins on endothelial cells and platelets. The released PDI reduces disulfide bonds on plasma vitronectin, enabling vitronectin to bind to αVβ3 and αIIbβ3...
February 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28214869/effects-of-antimalarial-tafenoquine-on-blood-platelet-activity-and-survival
#10
Hang Cao, Rosi Bissinger, Anja T Umbach, Abdulla Al Mamun Bhuyan, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The 8-aminoquinoline tafenoquine has been shown to be effective against Plasmodia, Leishmania and Trypanosoma. The substance is at least in part effective by triggering apoptosis of the parasites. Moreover, tafenoquine has been shown to trigger eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. The effect of tafenoquine on eryptosis is in part due to stimulation of Ca2+ entry and oxidative stress...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28195700/discovery-and-characterization-of-a-potent-and-specific-peptide-ligand-targeting-endothelial-progenitor-cells-and-endothelial-cells-for-tissue-regeneration
#11
Dake Hao, Wenwu Xiao, Ruiwu Liu, Priyadarsini Kumar, Yuanpei Li, Ping Zhou, Fuzheng Guo, Diana L Farmer, Kit S Lam, Fengshan Wang, Aijun Wang
Endothelial progenitor cells (EPCs) and endothelial cells (ECs) play a vital role in endothelialization and vascularization for tissue regeneration. Various EPC/EC targeting biomolecules have been investigated to improve tissue regeneration with limited success often due to their limited functional specificity and structural stability. One-bead one-compound (OBOC) combinatorial technology is an ultrahigh throughput chemical library synthesis and screening method suitable for ligand discovery against a wide range of biological targets, such as integrins...
March 2, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28194217/schisandra-chinensis-and-morus-alba-synergistically-inhibit-in-vivo-thrombus-formation-and-platelet-aggregation-by-impairing-the-glycoprotein-vi-pathway
#12
Dong-Seon Kim, Muhammad Irfan, Yoon-Young Sung, Seung Hyung Kim, Sun Haeng Park, Young Hyun Choi, Man Hee Rhee, Ho Kyoung Kim
Morus alba L. (MAL) extract has been used in traditional medicine for its cardioprotective and antiplatelet effects, while another herbal remedy, Schisandra chinensis (SCC), has been reported to have anti-inflammatory and antioxidant properties. We evaluated underlying cellular changes exerted by extracts of these plants on platelet function and effects of SCC + MAL on in vivo thrombus formation using AV shunt and tail thrombosis-length models in rats. In vitro platelet aggregation, granule secretion, and [Ca(2+)] i release assays were carried out...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28192121/convulxin-a-c-type-lectin-like-protein-inhibits-hcasmcs-functions-via-wad-motif-integrin-%C3%AE-v-interaction-and-nf-%C3%AE%C2%BAb-independent-gene-suppression-of-gro-and-il-8
#13
Chun-Ho Shih, Tin-Bin Chiang, Wen-Jeng Wang
Convulxin (CVX), a C-type lectin-like protein (CLPs), is a potent platelet aggregation inducer. To evaluate its potential applications in angiogenic diseases, the multimeric CVX were further explored on its mode of actions toward human coronary artery smooth muscle cells (HCASMCs). The N-terminus of β-chain of CVX (CVX-β) contains a putative disintegrin-like domain with a conserved motif upon the sequence comparison with other CLPs. Importantly, native CVX had no cytotoxic activity as examined by electrophoretic pattern...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28174163/platelets-and-von-willebrand-factor-in-atherogenesis
#14
Melinda D Wu, Tamara M Atkinson, Jonathan R Lindner
The role of platelet adhesion, activation and aggregation in acute atherothrombotic events such as myocardial infarction and stroke is well-established. There is increasing evidence that platelet-endothelial interactions also contribute to early atherosclerotic plaque initiation and growth. Through these interactions, platelet-derived factors can contribute to the pro-inflammatory and mitogenic status of resident mural cells. Among the many putative mechanisms for platelet-endothelial interactions, increased endothelial-associated Von Willebrand factor, particularly in a multimerized form, which interacts with platelet GPIbα and integrins is a major factor, and represents a therapeutic target for early atherogenesis...
February 7, 2017: Blood
https://www.readbyqxmd.com/read/28166238/integrin-dependent-cell-adhesion-to-neutrophil-extracellular-traps-through-engagement-of-fibronectin-in-neutrophil-like-cells
#15
Marcello Monti, Francesca Iommelli, Viviana De Rosa, Maria Vincenza Carriero, Roberta Miceli, Rosa Camerlingo, Giovanni Di Minno, Silvana Del Vecchio
Neutrophil extracellular traps (NETs), originally recognized as a host defense mechanism, were reported to promote thrombosis and metastatic dissemination of cancer cells. Here we tested the role of integrins α5β1 and ανβ3 in the adhesion of cancer cells to NETs. Neutrophil-like cells stimulated with calcium ionophore (A23187) were used as a stable source of cell-free NETs-enriched suspensions. Using NETs as an adhesion substrate, two human K562 cell lines, differentially expressing α5β1 and ανβ3 integrins, were subjected to adhesion assays in the presence or absence of DNAse 1, blocking antibodies against α5β1 or ανβ3, alone or in combination with DNAse 1, and Proteinase K...
2017: PloS One
https://www.readbyqxmd.com/read/28160743/dioxolanea3-phosphatidylethanolamines-are-generated-by-human-platelets-and-stimulate-neutrophil-integrin-expression
#16
Maceler Aldrovandi, Christine Hinz, Sarah N Lauder, Helen Podmore, Martin Hornshaw, David A Slatter, Victoria J Tyrrell, Stephen R Clark, Lawrence J Marnett, Peter W Collins, Robert C Murphy, Valerie B O'Donnell
Activated platelets generate an eicosanoid proposed to be 8-hydroxy-9,10-dioxolane A3 (DXA3). Herein, we demonstrate that significant amounts of DXA3 are rapidly attached to phosphatidylethanolamine (PE) forming four esterified eicosanoids, 16:0p, 18:0p, 18:1p and 18:0a/DXA3-PEs that can activate neutrophil integrin expression. These lipids comprise the majority of DXA3 generated by platelets, are formed in ng amounts (24.3±6.1ng/2×10(8)) and remain membrane bound. Pharmacological studies revealed DXA3-PE formation involves cyclooxygenase-1 (COX), protease-activated receptors (PAR) 1 and 4, cytosolic phospholipase A2 (cPLA2), phospholipase C and intracellular calcium...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28155614/cartilage-oligomeric-matrix-protein-matricellular-and-matricrine-signaling-in-cardiovascular-homeostasis-and-disease
#17
Yi Fu, Wei Kong
Cardiovascular (CV) diseases remain a leading cause of morbidity and mortality in the world. Increasing the understanding of the pathogenesis of various CV diseases may provide novel therapeutic targets to improve their prevention and treatment. Cartilage oligomeric matrix protein (COMP), also known as thrombospondin-5 (TSP-5), is a matricellular protein that is abundantly expressed in both cartilage and the CV system. Our group and others have identified COMP as playing critical roles in maintaining CV homeostasis...
February 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28148841/platelet-localized-fxi-promotes-a-vascular-coagulation-inflammatory-circuit-in-arterial-hypertension
#18
Sabine Kossmann, Jeremy Lagrange, Sven Jäckel, Kerstin Jurk, Moritz Ehlken, Tanja Schönfelder, Yvonne Weihert, Maike Knorr, Moritz Brandt, Ning Xia, Huige Li, Andreas Daiber, Matthias Oelze, Christoph Reinhardt, Karl Lackner, Andras Gruber, Brett Monia, Susanne H Karbach, Ulrich Walter, Zaverio M Ruggeri, Thomas Renné, Wolfram Ruf, Thomas Münzel, Philip Wenzel
Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function...
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28136130/integrin-%C3%AE-8-is-abundant-in-human-rat-and-mouse-trophoblasts
#19
Sebastian Herdl, Hanna Huebner, Gudrun Volkert, Ines Marek, Carlos Menendez-Castro, Stephanie C Noegel, Matthias Ruebner, Wolfgang Rascher, Andrea Hartner, Fabian B Fahlbusch
OBJECTIVE: Integrins exert regulatory functions in placentogenesis. Null mutation of certain integrin α subunits leads to placental defects with subsequent fetal growth restriction or embryonic lethality in mice. So far, the placental role of α8 integrin remains to be determined. METHODS: Localization of α8 integrin and its ligands, fibronectin (FN) and osteopontin (OPN), was studied by immunohistochemistry in human, rat, and mouse placenta. The vascularization of the placental labyrinth layer of α8 integrin-deficient mice was determined by CD31 staining...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28123327/the-inhibitory-activity-of-ginsenoside-rp4-in-adenosine-diphosphate-induced-platelet-aggregation
#20
Young-Min Son, Da-Hye Jeong, Hwa-Jin Park, Man-Hee Rhee
BACKGROUND: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification...
January 2017: Journal of Ginseng Research
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