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Platelet integrin

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https://www.readbyqxmd.com/read/28726538/marked-bleeding-diathesis-in-patients-with-platelet-dysfunction-due-to-a-novel-mutation-in-rasgrp2-encoding-caldag-gefi-p-gly305asp
#1
Emilse Bermejo, Maria F Alberto, David S Paul, Aaron A Cook, Paquita Nurden, Analia Sanchez Luceros, Alan T Nurden, Wolfgang Bergmeier
Congenital platelet function disorders are often the result of defects in critical signal transduction pathways required for platelet adhesion and clot formation. Mutations affecting RASGRP2, the gene encoding the Rap GTPase activator, CalDAG-GEFI, give rise to a novel, and rare, group of platelet signal transduction abnormalities. We here report platelet function studies for two brothers (P1 and P2) expressing a novel variant of RASGRP2, CalDAG-GEFI(p.Gly305Asp). P1 and P2 have a lifelong history of bleeding with severe epistaxis successfully treated with platelet transfusions or rFVIIa...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28725968/microglial-mediated-pdgf-cc-activation-increases-cerebrovascular-permeability-during-ischemic-stroke
#2
Enming Joseph Su, Chunzhang Cao, Linda Fredriksson, Ingrid Nilsson, Christina Stefanitsch, Tamara K Stevenson, Juanjuan Zhao, Margret Ragsdale, Yu-Yo Sun, Manuel Yepes, Chia-Yi Kuan, Ulf Eriksson, Dudley K Strickland, Daniel A Lawrence, Li Zhang
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα)...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28717419/platelet-extracellular-vesicles-induce-a-pro-inflammatory-smooth-muscle-cell-phenotype
#3
Tanja Vajen, Birke J Benedikter, Alexandra C A Heinzmann, Elena M Vasina, Yvonne Henskens, Martin Parsons, Patricia B Maguire, Frank R Stassen, Johan W M Heemskerk, Leon J Schurgers, Rory R Koenen
Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin αIIbβ3, while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28714276/human-platelet-lysate-supports-the-formation-of-robust-human-periodontal-ligament-cell-sheets
#4
Bei-Min Tian, Rui-Xin Wu, Chun-Sheng Bi, Xiao-Tao He, Yuan Yin, Fa-Ming Chen
The use of stem cell-derived sheets has become increasingly common in a wide variety of biomedical applications. Although substantial evidence has demonstrated that human platelet lysate (PL) can be used for therapeutic cell expansion, either as a substitute for or as a supplement to xenogeneic fetal bovine serum (FBS), its impact on cell sheet production remains largely unexplored. In this study, we manufactured periodontal ligament stem cell (PDLSC) sheets in vitro by incubating PDLSCs in sheet-induction media supplemented with various ratios of PL and FBS, i...
July 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28711718/phospholipase-d1-is-a-regulator-of-platelet-mediated-inflammation
#5
Meike Klier, Nina Sarah Gowert, Sven Jäckel, Christoph Reinhardt, Margitta Elvers
Glycoprotein (GP)Ib is not only required for stable thrombus formation but for platelet-mediated inflammatory responses. Phospholipase (PL)D1 is essential for GPIb-dependent aggregate formation under high shear conditions while nothing is known about PLD1-induced regulation of GPIb in platelet-mediated inflammation and the underlying mechanisms. This study aimed to investigate the relevance of PLD1 for platelet-mediated endothelial and leukocyte recruitment and activation in vitro and in vivo. Pld1(-/-) platelets showed strongly reduced adhesion to TNFα stimulated endothelial cells (ECs) under high shear conditions ex vivo...
July 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28704418/the-coll%C3%AE-gen-iii-fibril-has-a-flexi-rod-structure-of-flexible-sequences-interspersed-with-rigid-bioactive-domains-including-two-with-hemostatic-roles
#6
J Des Parkin, James D San Antonio, Anton V Persikov, Hayat Dagher, Raymond Dalgleish, Shane T Jensen, Xavier Jeunemaitre, Judy Savige
Collagen III is critical to the integrity of blood vessels and distensible organs, and in hemostasis. Examination of the human collagen III interactome reveals a nearly identical structural arrangement and charge distribution pattern as for collagen I, with cell interaction domains, fibrillogenesis and enzyme cleavage domains, several major ligand-binding regions, and intermolecular crosslink sites at the same sites. These similarities allow heterotypic fibril formation with, and substitution by, collagen I in embryonic development and wound healing...
2017: PloS One
https://www.readbyqxmd.com/read/28704364/dramatic-and-concerted-conformational-changes-enable-rhodocetin-to-block-%C3%AE-2%C3%AE-1-integrin-selectively
#7
Johannes A Eble, Matthew McDougall, George L Orriss, Stephan Niland, Benjamin Johanningmeier, Gottfried Pohlentz, Markus Meier, Simone Karrasch, Maria Inacia Estevão-Costa, Augusto Martins Lima, Jörg Stetefeld
The collagen binding integrin α2β1 plays a crucial role in hemostasis, fibrosis, and cancer progression amongst others. It is specifically inhibited by rhodocetin (RC), a C-type lectin-related protein (CLRP) found in Malayan pit viper (Calloselasma rhodostoma) venom. The structure of RC alone reveals a heterotetramer arranged as an αβ and γδ subunit in a cruciform shape. RC specifically binds to the collagen binding A-domain of the integrin α2 subunit, thereby blocking collagen-induced platelet aggregation...
July 2017: PLoS Biology
https://www.readbyqxmd.com/read/28697175/platelet-releasate-promotes-breast-cancer-growth-and-angiogenesis-via-vegf-integrin-cooperative-signalling
#8
Lei Jiang, Yun Luan, Xinyan Miao, Chao Sun, Kailin Li, Zhangsen Huang, Dawei Xu, Mingxiang Zhang, Feng Kong, Nailin Li
BACKGROUND: Selective platelet release of pro- or anti-angiogenic factors distinctly regulated angiogenesis. We hypothesised that selective release of platelet angiogenic factors could differently regulate tumour growth. METHODS: Breast cancer cell proliferation, cancer cell-induced endothelial tube formation in vitro, and tumour growth in vivo were studied in the presence of protease-activated receptor 1-stimulated platelet releasate (PAR1-PR; rich in pro-angiogenic factors) or PAR4-PR (rich in anti-angiogenic factors)...
July 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28694685/differential-effect-of-platelet-rich-plasma-fractions-on-%C3%AE-1-integrin-signaling-collagen-biosynthesis-and-prolidase-activity-in-human-skin-fibroblasts
#9
Tomasz Guszczyn, Arkadiusz Surażyński, Ilona Zaręba, Edyta Rysiak, Janusz Popko, Jerzy Pałka
The study was conducted to evaluate the effects of platelet-rich plasma (PRP), supernatant of PRP (SPRP) obtained by centrifugation, and supernatant of activated PRP (SActi-PRP) obtained by Ca(2+) solution-treated PRP on collagen biosynthesis, prolidase activity, and β1-integrin signaling in cultured human skin fibroblasts. Incubation of fibroblasts with 5% PRP for 24 h contributed to ~5-fold increase in collagen biosynthesis compared to the control. In the cells treated with 5% of SPRP or SActi-PRP, collagen biosynthesis showed a 3-fold increase of the control...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28694452/phosphatidylserine-mediated-platelet-clearance-by-endothelium-decreases-platelet-aggregates-and-procoagulant-activity-in-sepsis
#10
Ruishuang Ma, Rui Xie, Chengyuan Yu, Yu Si, Xiaoming Wu, Lu Zhao, Zhipeng Yao, Shaohong Fang, He Chen, Valerie Novakovic, Chunyan Gao, Junjie Kou, Yayan Bi, Hemant S Thatte, Bo Yu, Shufen Yang, Jin Zhou, Jialan Shi
The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693196/early-diagnosis-of-venous-thromboembolism-as-a-clinical-primary-symptom-of-occult-cancer-core-proteins-of-a-venous-thrombus
#11
Siwan Wen, Qianglin Duan, Fan Yang, Guiyuan Li, Lemin Wang
Malignancy is one of the risk factors of venous thromboembolism (VTE). As a common accompanying factor of malignant tumors, almost 20% of idiopathic VTEs are identified in patients with occult types of cancer as the primary symptom. The type of internal association that exists between malignant tumors and VTE has not yet been determined. The present review discusses the following: i) Reversible combinations between core proteins of venous thrombi and their ligand proteins. With the condition of immune cell balancing function collapse, which is characterized as dysfunction immune cells and impaired immune functions, the human body loses the function of eliminating infectious/malignant cells quickly and effectively...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693022/temsirolimus-sensitive-stimulation-of-platelet-activity-apoptosis-and-aggregation-by-collagen-related-peptide
#12
Hang Cao, Rosi Bissinger, Anja T Umbach, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus stimulates apoptosis of tumor cells and is thus therapeutically used for the treatment of diverse malignancies. On the other hand, temsirolimus has been shown to protect against apoptosis of hippocampal neurons. Similar to nucleated cells, blood platelets may enter suicidal death characterized by cell shrinkage and cell membrane scrambling. Platelet apoptosis is frequently preceded by Ca2+ entry, degranulation, integrin activation and stimulation of caspases...
July 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28692777/simultaneous-flow-cytometric-analysis-of-megakaryocyte-polyploidy-and-a-labile-intracellular-protein-using-zinc-based-fixation
#13
Jacqueline M Gertz, Megan Meuser, Beth A Bouchard
Differentiating megakaryocytes undergo a unique endomitotic cell cycle leading to large polyploidal cells, which fragment to generate platelets, blood cells important for normal hemostasis. Simultaneous assessment of DNA content and cellular proteins by flow cytometry is a useful tool to study megakaryocyte differentiation and to define expression of proteins important for megakaryocyte development and platelet formation. The usefulness of zinc salt-based fixation (ZBF), a non-crosslinking method of cell fixation that permits downstream analysis of nucleic acids (Jensen et al...
July 10, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28681242/the-potential-role-of-platelets-in-the-consensus-molecular-subtypes-of-colorectal-cancer
#14
REVIEW
Michael Lam, Jason Roszik, Preeti Kanikarla-Marie, Jennifer S Davis, Jeffrey Morris, Scott Kopetz, David G Menter
The consensus molecular subtypes (CMS) in colorectal cancer (CRC) represent distinct molecular subcategories of disease as reflected by comprehensive molecular profiling. The four CMS subtypes represent unique biology. CMS1 represents high immune infiltration. CMS2 demonstrates upregulation of canonical pathways such as WNT signaling. Widespread metabolic changes are seen in CMS3. CMS4 represents a mesenchymal phenotype with hallmark features including complement activation, matrix remodeling, angiogenesis, epithelial-mesechymal transition (EMT), integrin upregulation and stromal infiltration...
July 6, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28675156/corrigendum-leukocyte-integrin-mac-1-regulates-thrombosis-via-interaction-with-platelet-gpib%C3%AE
#15
Yunmei Wang, Huiyun Gao, Can Shi, Paul W Erhardt, Alexander Pavlovsky, Dmitry A Soloviev, Kamila Bledzka, Valentin Ustinov, Liang Zhu, Jun Qin, Adam D Munday, Jose Lopez, Edward Plow, Daniel I Simon
This corrects the article DOI: 10.1038/ncomms15559.
July 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28663280/megakaryocytic-smad4-regulates-platelet-function-through-syk-and-rock2-expression
#16
Yanhua Wang, Lirong Jiang, Xi Mo, Yu Lan, Xiao Yang, Xinyi Liu, Jian Zhang, Li Zhu, Junling Liu, Xiaolin Wu
Smad4, a key transcription factor in the TGF-β signaling pathway, is involved in a variety of cell physiological and pathological processes. Here, we characterized megakaryocyte/platelet-specific Smad4 deficiency in mice to elucidate its effect on platelet function. We found that megakaryocyte/platelet-specific loss of Smad4 caused mild thrombocytopenia and significantly extended first occlusion time and tail bleeding time in mice. Smad4-deficient platelets showed reduced agonist-induced platelet aggregation...
June 29, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28663253/inner-mitochondrial-membrane-disruption-links-apoptotic-and-agonist-initiated-phosphatidylserine-externalization-in-platelets
#17
Hyo-Jung Choo, Andaleb Kholmukhamedov, ChengZing Zhou, Shawn Jobe
OBJECTIVE: Phosphatidylserine exposure mediates platelet procoagulant function and regulates platelet life span. Apoptotic, necrotic, and integrin-mediated mechanisms have been implicated as intracellular determinants of platelet phosphatidylserine exposure. Here, we investigate (1) the role of mitochondrial events in platelet phosphatidylserine exposure initiated by these distinct stimuli and (2) the cellular interactions of the procoagulant platelet in vitro and in vivo. APPROACH AND RESULTS: Key mitochondrial events were examined, including cytochrome c release and inner mitochondrial membrane (IMM) disruption...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28660968/application-of-a-strain-rate-gradient-microfluidic-device-to-von-willebrand-s-disease-screening
#18
Rose J Brazilek, Francisco J Tovar-Lopez, Angus K T Wong, Huyen Tran, Amanda S Davis, James D McFadyen, Zane Kaplan, Sanjeev Chunilal, Shaun P Jackson, Harshal Nandurkar, Arnan Mitchell, Warwick S Nesbitt
Von Willebrand's disease (VWD) is the most common inherited bleeding disorder caused by either quantitative or qualitative defects of von Willebrand factor (VWF). Current tests for VWD require relatively large blood volumes, have low throughput, are time-consuming, and do not incorporate the physiologically relevant effects of haemodynamic forces. We developed a microfluidic device incorporating micro-contractions that harnesses well-defined haemodynamic strain gradients to initiate platelet aggregation in citrated whole blood...
June 29, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28652403/protease-activated-receptor-4-and-p2y12-dimerize-co-internalize-and-activate-akt-signaling-via-endosomal-recruitment-of-%C3%AE-arrestin
#19
Thomas H Smith, Julia G Li, Michael R Dores, JoAnn Trejo
Vascular inflammation and thrombosis requires the concerted actions of several different agonists, many of which act on G protein-coupled receptors (GPCRs). GPCR dimerization is a well-established phenomenon that can alter protomer function. In platelets and other cell types, protease-activated receptor-4 (PAR4) has been shown to dimerize with the purinergic receptor P2Y12 to coordinate β-arrestin-mediated Akt signaling, an important mediator of integrin activation. However, the mechanism by which the PAR4-P2Y12 dimer controls β-arrestin dependent Akt signaling is not known...
June 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28641286/effect-of-bexarotene-on-platelet-activation-and-apoptosis
#20
Hang Cao, Rosi Bissinger, Anja T Umbach, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The retinoid X receptor (RXRs) stimulator Bexarotene ((4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl] benzoic acid) is used for the treatment of several malignancies. Bexarotene is at least in part effective by stimulation of apoptosis of tumor cells. Moreover, Bexarotene triggers eryptosis, the suicidal death of erythrocytes. Similar to erythrocytes, blood platelets lack nuclei but are nevertheless able to enter an apoptosis-like phenotype, characterized by caspase activation, cell shrinkage and cell membrane scrambling with phospha-tidylserine translocation to the cell surface...
2017: Cellular Physiology and Biochemistry
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