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Platelet hyperactivation

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https://www.readbyqxmd.com/read/28637879/platelets-express-activated-p2y12-receptor-in-patients-with-diabetes
#1
Liang Hu, Lin Chang, Yan Zhang, Lili Zhai, Shenghui Zhang, Zhiyong Qi, Hongmei Yan, Yan Yan, Xinping Luo, Si Zhang, Yiping Wang, Satya P Kunapuli, Hongying Ye, Zhongren Ding
Background -Platelets from patients with diabetes are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes. However, the underlying mechanism of hyperactivated platelets is not completely understood. Methods -We measured P2Y12 expression on platelets from patients with type 2 diabetes mellitus (T2DM) and on platelets from rats with diabetes. We also assayed platelet P2Y12 activation by measuring cAMP and VASP phosphorylation...
June 21, 2017: Circulation
https://www.readbyqxmd.com/read/28614772/inhibition-of-blood-platelet-adhesion-by-phenolics-rich-fraction-of-hippophae-rhamnoides-l-fruits
#2
B Olas, B Kontek, M Szczesna, L Grabarczyk, A Stochmal, J Zuchowski
Beneficial influence of fruits on human health may be their ability to prevent the hyperactivation of blood platelets and cardiovascular disorders. Effects of the phenolic fraction from Hippophae rhamnoides fruit on different stages of blood platelet activation (platelet adhesion and aggregation) were studied in vitro. We also examined effects of the H. rhamnoides fraction on metabolism of thiol groups, which plays an important role in platelet functions. The effects of the H. rhamnoides fraction on adhesion of blood platelets to collagen and fibrinogen were determined with Tuszynski's and Murphy's method...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28528289/platelet-hyperactivation-apoptosis-and-hypercoagulability-in-patients-with-acute-pulmonary-embolism
#3
Samin Rezania, Michael A Puskarich, Daniela N Petrusca, Evandro M Neto-Neves, Matthew T Rondina, Jeffrey A Kline
Changes in systemic redox balance can alter platelet activation and aggregation. Acute pulmonary embolism (PE) is a systematic inflammatory disease associated with mechanical shear stress, increased thrombin, catecholamines, serotonin and hemolysis, which cumulatively can hyperactivate platelets and accelerate their turnover. We tested the hypothesis that platelets from patients with moderately severe PE will show hyperstimulation and a pre-apoptotic phenotype associated with microparticles (MPs) in plasma...
July 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28501760/stromal-pdgfr-%C3%AE-activation-enhances-matrix-stiffness-impedes-mammary-ductal-development-and-accelerates-tumor-growth
#4
Anisha M Hammer, Gina M Sizemore, Vasudha C Shukla, Alex Avendano, Steven T Sizemore, Jonathan J Chang, Raleigh D Kladney, Maria C Cuitiño, Katie A Thies, Quinn Verfurth, Arnab Chakravarti, Lisa D Yee, Gustavo Leone, Jonathan W Song, Samir N Ghadiali, Michael C Ostrowski
The extracellular matrix (ECM) is critical for mammary ductal development and differentiation, but how mammary fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model to activate platelet derived growth factor receptor-alpha (PDGFRα) specifically in the stroma. Hyperactivation of PDGFRα in the mammary stroma severely hindered pubertal mammary ductal morphogenesis, but did not interrupt the lobuloalveolar differentiation program. Increased stromal PDGFRα signaling induced mammary fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid (HA) and collagen deposition...
June 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28480270/a-randomized-placebo-controlled-trial-of-aspirin-effects-on-immune-activation-in-chronically-human-immunodeficiency-virus-infected-adults-on-virologically-suppressive-antiretroviral-therapy
#5
Meagan P O'Brien, Peter W Hunt, Douglas W Kitch, Karin Klingman, James H Stein, Nicholas T Funderburg, Jeffrey S Berger, Pablo Tebas, Brian Clagett, Daniela Moisi, Netanya S Utay, Fran Aweeka, Judith A Aberg
BACKGROUND: Immune activation persists despite suppressive antiretroviral therapy (ART) in human immunodeficiency virus (HIV) infection and predicts non-Acquired Immune Deficiency Syndrome (AIDS) comorbidities including cardiovascular disease. Activated platelets play a key role in atherothrombosis and inflammation, and platelets are hyperactivated in chronic HIV infection. Aspirin is a potent inhibitor of platelet activation through the cyclooxygenase-1 (COX-1) pathway. We hypothesized that platelet activation contributes to immune activation and that aspirin would reduce immune activation and improve endothelial function in ART-suppressed HIV-infected individuals...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28412372/flavonoids-and-platelet-aggregation-a-brief-review
#6
REVIEW
Caterina Faggio, Antoni Sureda, Silvia Morabito, Ana Sanches-Silva, Andrei Mocan, Seyed Fazel Nabavi, Seyed Mohammad Nabavi
Platelets are small anucleated fragments derived from a megakaryocyte precursor. Platelets play a key role in many physiological functions especially in hemostasis and wound healing processes in order to maintain the integrity of the circulatory system. In addition, activated platelets release cytokines and chemokines which modulate the immune response and, in some cases of hyperactivation, they could be associated to the pathogenesis of inflammatory diseases. Flavonoids are polyphenolic compounds ubiquosly found in plants known to be potent antioxidants with positive effects against diverse diseases such as cancer, neurodegenerative or cardiovascular disease...
July 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28300459/mildly-elevated-unconjugated-bilirubin-is-associated-with-reduced-platelet-activation-related-thrombogenesis-and-inflammation-in-gilbert-s-syndrome
#7
Avinash R Kundur, Abishek B Santhakumar, Andrew C Bulmer, Indu Singh
Gilbert's syndrome (GS) is associated with a mild unconjugated hyperbilirubinemia, increased circulating antioxidant capacity, and reduced cardiovascular disease (CVD) risk. The current study investigated whether mildly elevated circulating unconjugated bilirubin (UCB) is negatively associated with multiple thrombotic risk factors including platelet activity, hemostatic function, and inflammation in individuals with GS. Blood samples were collected from matched GS and control subjects (14 per group). Activation-dependent platelet surface marker expression of PAC-1 (binds to GPIIb/IIIa surface receptors on activated platelets) and CD62P (marker for P-selectin released from activated degranulated platelets) was assessed in adenosine diphosphate (ADP)-stimulated platelets using flow cytometry...
March 16, 2017: Platelets
https://www.readbyqxmd.com/read/27487510/evaluation-of-bone-marrow-with-particular-consideration-of-the-megakaryocyte-lineage-and-coagulation-profile-in-the-pregnant-fallow-deer-dama-dama
#8
A Snarska, P Sobiech
The aim of the study was to evaluate the megakaryocyte lineage of bone marrow and coagulation parameters in fallow deer during the last month of pregnancy. The animals were managed in the barn-feeding system. Twenty female fallow deer, aged 2-3 years, divided into 2 groups were used in the study. Group 1 comprised the females in the last month of pregnancy, and the non-pregnant females were used as the control. All the animals were clinically healthy. Coagulation parameters were measured in all the deer: thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), and plasma concentrations of fibrinogen, D-dimer, and antithrombin III...
2016: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/27389715/cooperation-of-germ-line-jak2-mutations-e846d-and-r1063h-in-hereditary-erythrocytosis-with-megakaryocytic-atypia
#9
Katarina Kapralova, Monika Horvathova, Christian Pecquet, Jana Fialova Kucerova, Dagmar Pospisilova, Emilie Leroy, Barbora Kralova, Jelena D Milosevic Feenstra, Fiorella Schischlik, Robert Kralovics, Stefan N Constantinescu, Vladimir Divoky
The role of somatic JAK2 mutations in clonal myeloproliferative neoplasms (MPNs) is well established. Recently, germ line JAK2 mutations were associated with polyclonal hereditary thrombocytosis and triple-negative MPNs. We studied a patient who inherited 2 heterozygous JAK2 mutations, E846D from the mother and R1063H from the father, and exhibited erythrocytosis and megakaryocytic atypia but normal platelet number. Culture of erythroid progenitors from the patient and his parents revealed hypersensitivity to erythropoietin (EPO)...
September 8, 2016: Blood
https://www.readbyqxmd.com/read/27312156/imbalanced-immune-homeostasis-in-immune-thrombocytopenia
#10
Karina Yazdanbakhsh
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued...
April 2016: Seminars in Hematology
https://www.readbyqxmd.com/read/27058300/lovastatin-corrects-erk-pathway-hyperactivation-in-fragile-x-syndrome-potential-of-platelet-s-signaling-cascades-as-new-outcome-measures-in-clinical-trials
#11
David Pellerin, Artuela Çaku, Mathieu Fradet, Paméla Bouvier, Jean Dubé, François Corbin
AIM: To establish whether platelets from fragile X syndrome (FXS) individuals recapitulate FXS mouse neurons' defects in ERK and Akt pathways, and to evaluate the effect of lovastatin on these pathways. METHODS: ERK and Akt phosphorylation (pERK, pAkt) statuses were assessed with quantitative Western blotting before and after a 12-week lovastatin trial. RESULTS: Levels of pERK and pAkt were increased in FXS platelets, and lovastatin specifically normalized ERK activity...
September 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/26511074/coagulation-activation-in-sickle-cell-trait-an-exploratory-study
#12
COMPARATIVE STUDY
Chirag Amin, Soheir Adam, Micah J Mooberry, Abdullah Kutlar, Ferdane Kutlar, Denise Esserman, Julia E Brittain, Kenneth I Ataga, Jen-Yea Chang, Alisa S Wolberg, Nigel S Key
Recent epidemiologic data suggest that sickle cell trait (HbAS; AS) is a risk factor for venous thromboembolism. We conducted an exploratory study of healthy subjects with AS under baseline conditions to determine whether a chronic basal hyperactivation of coagulation exists, and if so, what mechanism(s) contribute to this state. Eighteen healthy AS individuals were compared to 22 African-American controls with a normal haemoglobin profile (HbAA; AA) and 17 patients with sickle cell disease (HbSS; SS). Plasma thrombin-antithrombin complexes and D-dimer levels were elevated in AS relative to AA patients (P = 0·0385 and P = 0·017, respectively), and as expected, were much higher in SSversusAA (P < 0·0001 for both)...
November 2015: British Journal of Haematology
https://www.readbyqxmd.com/read/26508555/a-unique-snare-machinery-for-exocytosis-of-cytotoxic-granules-and-platelets-granules
#13
REVIEW
Bor Luen Tang
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells target infected or transformed cells with perforin-containing cytotoxic granules through immune synapses, while platelets secrete several types of granules which contents are essential for thrombosis and hemostasis. Recent work has culminated in the notion that an exocytic SNARE complex, based on a very similar set of components, is primarily responsible for exocytosis of the diverse granules in these different cell types. Granule exocytosis is, in particular, uniquely dependent on the atypical Q-SNARE syntaxin 11, its interacting partners of the Sec/Munc (SM) family, and is regulated by Rab27a...
2015: Molecular Membrane Biology
https://www.readbyqxmd.com/read/25902782/loss-of-the-insulin-receptor-in-murine-megakaryocytes-platelets-causes-thrombocytosis-and-alterations-in-igf-signalling
#14
Samantha F Moore, Christopher M Williams, Edward Brown, Thomas A Blair, Matthew T Harper, Richard J Coward, Alastair W Poole, Ingeborg Hers
AIMS: Patients with conditions that are associated with insulin resistance such as obesity, type 2 diabetes mellitus, and polycystic ovary syndrome have an increased risk of thrombosis and a concurrent hyperactive platelet phenotype. Our aim was to determine whether insulin resistance of megakaryocytes/platelets promotes platelet hyperactivation. METHODS AND RESULTS: We generated a conditional mouse model where the insulin receptor (IR) was specifically knocked out in megakaryocytes/platelets and performed ex vivo platelet activation studies in wild-type (WT) and IR-deficient platelets by measuring aggregation, integrin αIIbβ3 activation, and dense and α-granule secretion...
July 1, 2015: Cardiovascular Research
https://www.readbyqxmd.com/read/25897353/endothelial-and-platelet-markers-in-diabetes-mellitus-type-2
#15
REVIEW
Peter Kubisz, Lucia Stančiaková, Ján Staško, Peter Galajda, Marián Mokáň
Diabetes mellitus (DM) is an extremely common disorder which carries a risk of vascular impairment. DM type 2 (DM2) can be characterized by the dysfunction of haemostasis manifesting by stimulated coagulation process, disorder of platelet function and decreased fibrinolytic activity. These all are the reasons why DM2 is the most common acquired thrombophilia. Endothelial dysfunction along with platelet hyperactivity are unquestionably involved in the hyperactivation of platelets and clotting factors in DM. As a natural consequence of continuous investigation, many markers of endothelial dysfunction and diabetic thrombocytopathy have been identified and considered for implementation in clinical practice...
April 15, 2015: World Journal of Diabetes
https://www.readbyqxmd.com/read/25877374/geometric-complexity-identifies-platelet-activation-in-familial-hypercholesterolemic-patients
#16
Giorgio Bianciardi, Margherita Aglianò, Nila Volpi, Claudia Stefanutti
Familial hypercholesterolemia (FH), a genetic disease, is associated with a severe incidence of athero-thrombotic events, related, also, to platelet hyperreactivity. A plethora of methods have been proposed to identify those activated circulating platelets, none of these has proved really effective. We need efficient methods to identify the circulating platelet status in order to follow the patients after therapeutic procedures. We propose the use of computerized fractal analysis for an objective characterization of the complexity of circulating platelet shapes observed by means of transmission electron microscopy in order to characterize the in vivo hyperactivated platelets of familial hypercholesterolemic patients, distinguishing them from the in vivo resting platelets of healthy individuals...
June 2015: Microscopy Research and Technique
https://www.readbyqxmd.com/read/25832443/moderate-oral-supplementation-with-docosahexaenoic-acid-improves-platelet-function-and-oxidative-stress-in-type-2-diabetic-patients
#17
RANDOMIZED CONTROLLED TRIAL
E Véricel, R Colas, C Calzada, Q H Lê, N Feugier, C Cugnet, H Vidal, M Laville, P Moulin, M Lagarde
Platelets from patients with type 2 diabetes are characterised by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes. We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (n=11 post-menopausal women with type 2 diabetes) to test the effects of 400 mg/day of DHA intake for two weeks on platelet aggregation, markers of arachidonic acid metabolism, lipid peroxidation status, and lipid composition...
August 2015: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/25761116/%C3%AE-synuclein-induced-synapse-damage-in-cultured-neurons-is-mediated-by-cholesterol-sensitive-activation-of-cytoplasmic-phospholipase-a2
#18
Clive Bate, Alun Williams
The accumulation of aggregated forms of the α-synuclein (αSN) is associated with the pathogenesis of Parkinson's disease (PD) and Dementia with Lewy Bodies. The loss of synapses is an important event in the pathogenesis of these diseases. Here we show that aggregated recombinant human αSN, but not βSN, triggered synapse damage in cultured neurons as measured by the loss of synaptic proteins. Pre-treatment with the selective cytoplasmic phospholipase A2 (cPLA2) inhibitors AACOCF3 and MAFP protected neurons against αSN-induced synapse damage...
2015: Biomolecules
https://www.readbyqxmd.com/read/25601838/platelet-hemostasis-in-patients-with-metabolic-syndrome-and-type-2-diabetes-mellitus-cgmp-and-no-dependent-mechanisms-in-the-insulin-mediated-platelet-aggregation
#19
REVIEW
Tatiana E Suslova, Alexei V Sitozhevskii, Oksana N Ogurkova, Elena S Kravchenko, Irina V Kologrivova, Yana Anfinogenova, Rostislav S Karpov
Patients with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) have high risk of microcirculation complications and microangiopathies. An increase in thrombogenic risk is associated with platelet hyperaggregation, hypercoagulation, and hyperfibrinolysis. Factors leading to platelet activation in MetS and T2DM comprise insulin resistance, hyperglycemia, non-enzymatic glycosylation, oxidative stress, and inflammation. This review discusses the role of nitric oxide (NO) in the regulation of platelet adhesion and aggregation processes...
2014: Frontiers in Physiology
https://www.readbyqxmd.com/read/25325344/effect-of-acetylsalicylic-acid-on-platelet-activation-and-oxidative-profile-in-a-set-of-brazilian-patients-with-type-2-diabetes-mellitus
#20
Rita C F Duarte, Líllian H Gonçalves, Fernanda M F Campos, Olindo A M Filho, Michelle T Alves, Ana P Fernandes, Karina B G Borges, Luci M S Dusse, Mayara C Faria, Gisele S Gonçalves, Adriana A Bosco, Valéria C Sandrim, Maria G Carvalho
Type 2 diabetes mellitus (DM2) is a metabolic disorder associated with hyperactivation of platelets, increased formation of platelet microparticles (PMPs) and oxidative stress that are related to cardiovascular complications. Acetylsalicylic acid (ASA) is an antiplatelet agent used in the prevention of atherothrombosis. The aim of this study was to evaluate the effect of ASA by means of platelet activation and oxidative profile. We collected blood samples of 81 patients with DM2 before and during ASA treatment...
March 2015: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
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