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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
Satoshi Fujii, Tomonori Sugiura, Yasuaki Dohi, Nobuyuki Ohte
Atherosclerosis is one of the major causes of death. Data from animal experiments suggest that atherosclerosis involves an inflammatory process of the vascular wall under hyperlipidemia. Atherothrombosis can become a serious complication of atherosclerosis leading to acute cardiovascular events such as myocardial infarction and stroke. Clinical applications to use this knowledge remain scarce. The plasma levels of vascular endothelium-enriched microRNA (miRNAs) in patients with atherosclerotic vascular disease could serve as a disease marker...
2016: Thrombosis Journal
Olga Gruzdeva, Evgenya Uchasova, Yulia Dyleva, Olga Akbasheva, Victoria Karetnikova, Olga Barbarash
Dyslipidemia is one of the primary causes of cardiovascular disease. Therefore, attention has been focused on the development of drugs that normalize lipid levels and exert an effect on markers of atherothrombosis, insulin resistance (IR), and inflammation. Atorvastatin is a drug with not only lipid-lowering potential, but it has multiple non-lipid effects. This study aimed to evaluate atorvastatin effects on lipid, adipokine, IR, and inflammatory statuses in patients with myocardial infarction (MI) in an in-hospital setting...
2016: Frontiers in Pharmacology
Henry Hui, Kathy A Fuller, Wendy N Erber, Matthew D Linden
Platelets are subcellular blood elements with a well-established role in haemostasis. Upon activation platelets undergo granule exocytosis, resulting in α-granule P-Selectin being expressed on the cell membrane. This allows binding of activated platelets to P-Selectin glycoprotein ligand 1 (PSGL-1) expressing leukocytes, forming leukocyte-platelet aggregates (LPAs). Whole blood flow cytometry (FCM) has demonstrated that elevated circulating LPAs (especially monocyte LPAs) are linked to atherothrombosis in high risk patients, and that activated platelet binding influences monocytes towards a pro-adhesive and pro-atherogenic phenotype...
October 5, 2016: Methods: a Companion to Methods in Enzymology
Francesca Santilli, Rossella Liani, Patrizia Di Fulvio, Gloria Formoso, Paola Simeone, Romina Tripaldi, Thor Ueland, Pål Aukrust, Giovanni Davì
Resistin is an adipokine that promotes inflammation and insulin resistance by targeting several cells including platelets. We hypothesised that in type 2 diabetes (T2DM), resistin may foster in vivo oxidative stress, thromboxane-dependent platelet activation and platelet-derived inflammatory proteins release, key determinants of atherothrombosis. A cross-sectional comparison of circulating resistin, sCD40L, as a marker of platelet-mediated inflammation, asymmetric dimethylarginine (ADMA), endothelial dysfunction marker, Dickkopf (DKK)-1, reflecting the inflammatory interaction between platelets and endothelial cells, and urinary 8-iso-PGF2α and 11-dehydro-TxB2, reflecting in vivo lipid peroxidation and platelet activation, respectively, was performed between 79 T2DM patients and 30 healthy subjects...
October 6, 2016: Thrombosis and Haemostasis
Riyaad Aungraheeta, Alexandra Conibear, Mark Butler, Eamonn Kelly, Sven Nylander, Andrew Mumford, Stuart Mundell
Ticagrelor is a potent antagonist of the P2Y12 receptor (P2Y12R) and consequently an inhibitor of platelet activity effective in the treatment of atherothrombosis. Here, we sought to further characterise its molecular mechanism of action. Initial studies showed that ticagrelor promoted a greater inhibition of ADP-induced Ca(2+) release in washed platelets versus other P2Y12R antagonists. This additional effect of ticagrelor beyond P2Y12R antagonism was in part as a consequence of ticagrelor inhibiting the equilibrative nucleoside transporter 1 (ENT1) on platelets, leading to accumulation of extracellular adenosine and activation of Gs-coupled adenosine A2A receptors...
September 30, 2016: Blood
Alon Eisen, Deepak L Bhatt, P Gabriel Steg, Kim A Eagle, Shinya Goto, Jianping Guo, Sidney C Smith, E Magnus Ohman, Benjamin M Scirica
BACKGROUND: The extent to which angina is associated with future cardiovascular events in patients with coronary artery disease has long been debated. METHODS AND RESULTS: Included were outpatients with established coronary artery disease who were enrolled in the REACH registry and were followed for 4 years. Angina at baseline was defined as necessitating episodic or permanent antianginal treatment. The primary end point was the composite of cardiovascular death, myocardial infarction, or stroke...
2016: Journal of the American Heart Association
Aparna Pandey, Amit Shrivastava, Ashok Solanki
BACKGROUND: Stroke is one of the most frequent causes of death and disability worldwide and has significant clinical and socioeconomic impact. Hyperlipidemia and inflammation play major roles in atherothrombosis and in stroke. This study is conducted to compare the high sensitive C-reactive protein (hs-CRP) levels and the lipid profile parameters between stroke patients and control group and demonstrate correlation between markers, neurological deficit, and short-term outcome. METHODS: We have studied a total 162 patients according to inclusion criteria...
July 6, 2016: Iranian Journal of Neurology
Birgit Markus, Karsten Grote, Michael Worsch, Behnoush Parviz, Andreas Boening, Bernhard Schieffer, Mariana S Parahuleva
OBJECTIVE: Stroke and transient ischemic attacks are considered as clinical manifestations of atherosclerotic disease due to on-going vascular inflammation and finally atherothrombosis of the carotid arteries. MicroRNAs (miRNA/miR) are known to be involved in vascular inflammation and plaque destabilization. The aim of this study was to analyze the expression profile of selected miRNAs in endarterectomy specimen from carotid arteries that were taken from patients with asymptomatic and symptomatic atherosclerotic plaques...
2016: PloS One
Lina Badimon, Rosa Suades, Eduardo Fuentes, Iván Palomo, Teresa Padró
Reports in the last decade have suggested that the role of platelets in atherosclerosis and its thrombotic complications may be mediated, in part, by local secretion of platelet-derived microvesicles (pMVs), small cell blebs released during the platelet activation process. MVs are the most abundant cell-derived microvesicle subtype in the circulation. High concentrations of circulating MVs have been reported in patients with atherosclerosis, acute vascular syndromes, and/or diabetes mellitus, suggesting a potential correlation between the quantity of microvesicles and the clinical severity of the atherosclerotic disease...
2016: Frontiers in Pharmacology
Emilie Montenont, Christina Echagarruga, Nicole Allen, Elisa Araldi, Yajaira Suarez, Jeffrey S Berger
Platelet activity plays a major role in hemostasis with increased platelet activity likely contributing to the pathogenesis of atherothrombosis. We sought to identify associations between platelet activity variability and platelet related genes in healthy controls. Transcriptional profiling of platelets revealed that WD-40 repeat domain 1 (WDR1), an enhancer of actin depolymerizing factor activity, is downregulated in platelet mRNA from subjects with a hyperreactive platelet phenotype. We used the human megakaryoblastic cell line MEG-01 as an in vitro model for human megakaryocytes and platelets...
September 8, 2016: Blood
Jérémie Abtan, Deepak L Bhatt, Yedid Elbez, Emmanuel Sorbets, Kim Eagle, Yasuo Ikeda, David Wu, Mary E Hanson, Hakima Hannachi, Puneet K Singhal, Philippe Gabriel Steg, Gregory Ducrocq
BACKGROUND: Although the rate of in-hospital ischemic events after myocardial infarction (MI) has dramatically decreased, long-term residual risk may remain substantial. However, most of the information on current residual risk is derived from highly selected randomized trials. HYPOTHESIS: In patients with previous MI and no prior ischemic stroke/transient ischemic attack (TIA), residual ischemic risk increases over time. METHODS: Using the international Reduction of Atherothrombosis for Continued Health (REACH) registry, we analyzed baseline characteristics and 4-year follow-up of patients with previous MI and no history of stroke/TIA to describe annual rates of recurrent ischemic events globally and by geography...
September 2, 2016: Clinical Cardiology
Saya Ozaki, Mie Kurata, Yoshiaki Kumon, Shirabe Matsumoto, Masahiko Tagawa, Hideaki Watanabe, Shiro Ohue, Jitsuo Higaki, Takanori Ohnishi
We investigated whether thrombin-cleaved osteopontin N-terminal is useful as a blood biomarker of acute atherothrombotic ischemic stroke. Acute ischemic stroke patients were prospectively evaluated with brain magnetic resonance imaging and cardiac evaluations for etiological diagnosis according to the Trial of Org 10172 in Acute Stroke Treatment classification. They were divided into the atherothrombotic and non-atherothrombotic groups. Thrombin-cleaved osteopontin N-terminal, osteopontin, matrix metalloproteinase-9, S100B, C-reactive protein and D-dimer levels were measured from blood samples collected at admission...
August 25, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Michal Kacprzak, Marzenna Zielinska
: Inflammation plays an important role on every stage of atherosclerosis. Myeloperoxidase (MPO), a leukocyte-derived enzyme that participates in the innate immunity, probably is involved in many stages of atherothrombosis. According to the recent studies, MPO is related with unfavorable outcome in patients with chest pain and acute coronary syndromes. Its role in prediction of outcomes after ST-segment elevation myocardial infarction (STEMI) remains unclear. The aim of the study was to assess if elevated MPO level is a predictor of long-term adverse cardiac events in patients with STEMI treated with primary percutaneous coronary intervention (pPCI)...
November 15, 2016: International Journal of Cardiology
Monica Verdoia, Patrizia Pergolini, Roberta Rolla, Chiara Sartori, Matteo Nardin, Alon Schaffer, Lucia Barbieri, Veronica Daffara, Paolo Marino, Giorgio Bellomo, Harry Suryapranata, Giuseppe De Luca
Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCIs). However, very few are known so far on the predictors of high-residual platelet reactivity (HRPR) despite antiplatelet strategies. Increasing attention has been paid in the last years to the role of vitamin D in atherothrombosis. Therefore, the aim of our study was to evaluate the impact of vitamin D levels on platelet function in patients treated with dual antiplatelet therapy (DAPT)...
September 2016: Platelets
Justin C Mason
The vascular endothelium is a critical interface, which separates the organs from the blood and its contents. The endothelium has a wide variety of functions and maintenance of endothelial homeostasis is a multi-dimensional active process, disruption of which has potentially deleterious consequences if not reversed. Vascular injury predisposes to endothelial apoptosis, dysfunction and development of atherosclerosis. Endothelial dysfunction is an end-point, a central feature of which is increased ROS generation, a reduction in endothelial nitric oxide synthase and increased nitric oxide consumption...
August 9, 2016: Vascular Pharmacology
Hugo Ten Cate, H Coenraad Hemker
No abstract text is available yet for this article.
August 2016: Journal of the American Heart Association
C Pérez-Sánchez, M A Aguirre, P Ruiz-Limón, N Barbarroja, Y Jiménez-Gómez, I Arias de la Rosa, A Rodriguez-Ariza, E Collantes-Estévez, P Segui, F Velasco, M J Cuadrado, R Teruel, R González-Conejero, C Martínez, Ch López-Pedrera
MicroRNAs markedly affect the immune system, and have a relevant role in CVD and autoimmune diseases. Yet, no study has analyzed their involvement in atherothrombosis related to APS and SLE patients. This study intended to: 1) identify and characterize microRNAs linked to CVD in APS and SLE; 2) assess the effects of specific autoantibodies. Six microRNAs, involved in atherothrombosis development, were quantified in purified leukocytes from 23 APS and 64 SLE patients, and 56 healthy donors. Levels of microRNAs in neutrophils were lower in APS and SLE than in healthy donors...
2016: Scientific Reports
Fleur M van der Valk, Siroon Bekkering, Jeffrey Kroon, Calvin Yeang, Jan Van den Bossche, Jaap D van Buul, Amir Ravandi, Aart J Nederveen, Hein J Verberne, Corey Scipione, Max Nieuwdorp, Leo A B Joosten, Mihai G Netea, Marlys L Koschinsky, Joseph L Witztum, Sotirios Tsimikas, Niels P Riksen, Erik S G Stroes
BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent cardiovascular risk factor, but the underlying mechanisms responsible for its pathogenicity are poorly defined. Because Lp(a) is the prominent carrier of proinflammatory oxidized phospholipids (OxPLs), part of its atherothrombosis might be mediated through this pathway. METHODS: In vivo imaging techniques including magnetic resonance imaging, (18)F-fluorodeoxyglucose uptake positron emission tomography/computed tomography and single-photon emission computed tomography/computed tomography were used to measure subsequently atherosclerotic burden, arterial wall inflammation, and monocyte trafficking to the arterial wall...
August 23, 2016: Circulation
Patrizia Amadio, Damiano Baldassarre, Leonardo Sandrini, Babette B Weksler, Elena Tremoli, Silvia S Barbieri
Cigarette smoke (CS) activates platelets, promotes vascular dysfunction, and enhances Tissue Factor (TF) expression in blood monocytes favoring pro-thrombotic states. Brain-derived neurotrophic factor (BDNF), a member of the family of neurotrophins involved in survival, growth, and maturation of neurons, is released by activated platelets (APLTs) and plays a role in the cardiovascular system. The effect of CS on circulating levels of BDNF is controversial and the function of circulating BDNF in atherothrombosis is not fully understood...
August 5, 2016: Platelets
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