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atherothrombosis

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https://www.readbyqxmd.com/read/28053157/blockade-of-protease-activated-receptor-4-par4-provides-robust-antithrombotic-activity-with-low-bleeding
#1
Pancras C Wong, Dietmar Seiffert, J Eileen Bird, Carol A Watson, Jeffrey S Bostwick, Mary Giancarli, Nick Allegretto, Ji Hua, David Harden, Jocelyne Guay, Mario Callejo, Michael M Miller, R Michael Lawrence, Jacques Banville, Julia Guy, Brad D Maxwell, E Scott Priestley, Anne Marinier, Ruth R Wexler, Michel Bouvier, David A Gordon, William A Schumacher, Jing Yang
Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4...
January 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28045401/therapeutic-approaches-targeting-inflammation-for-diabetes-and-associated-cardiovascular-risk
#2
Allison B Goldfine, Steven E Shoelson
Obesity-related sub-acute chronic inflammation has been associated with incident type 2 diabetes and atherosclerotic cardiovascular disease. Inflammation is increasingly considered to be a pathologic mediator of these commonly co-occurring diseases. A growing number of preclinical and clinical studies support the inflammatory hypothesis, but clinical trials to confirm the therapeutic potential to target inflammation to treat or prevent cardiometabolic conditions are still ongoing. There are multiple inflammatory signaling pathways...
January 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28012647/cd98-regulates-vascular-smooth-muscle-cell-proliferation-in-atherosclerosis
#3
Yvonne Baumer, Sara McCurdy, Martin Alcala, Nehal Mehta, Bog-Hieu Lee, Mark H Ginsberg, William A Boisvert
BACKGROUND AND AIMS: Vascular smooth muscle cells (VSMC) migrate and proliferate to form a stabilizing fibrous cap that encapsulates atherosclerotic plaques. CD98 is a transmembrane protein made of two subunits, CD98 heavy chain (CD98hc) and one of six light chains, and is known to be involved in cell proliferation and survival. Because the influence of CD98hc on atherosclerosis development is unknown, our aim was to determine if CD98hc expressed on VSMC plays a role in shaping the morphology of atherosclerotic plaques by regulating VSMC function...
November 16, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27988435/in-vivo-distribution-of-single-chain-variable-fragment-scfv-against-atherothrombotic-oxidized-ldl-%C3%AE-2-glycoprotein-i-complexes-into-atherosclerotic-plaques-of-whhl-rabbits-implication-for-clinical-pet-imaging
#4
REVIEW
Takanori Sasaki, Kazuko Kobayashi, Shoichi Kita, Kazuo Kojima, Hiroyuki Hirano, Lianhua Shen, Fumiaki Takenaka, Hiromi Kumon, Eiji Matsuura
BACKGROUND: Oxidized LDL (oxLDL) can exist as a complex with β2-glycoprotein I (β2GPI) in plasma/serum of patients with non-autoimmune atherosclerotic disease or antiphospholipid syndrome (APS). Nonetheless, direct in vivo evidence supporting the pathophysiological involvement of oxLDL/β2GPI complexes and specific autoantibody against the complexes in developing atherothrombosis has yet been established. In the present study, we demonstrated in vivo distribution of single chain variable fragment of IgG anti-oxLDL/β2GPI complexes (3H3-scFv) in Watanabe heritable hyperlipidemic (WHHL) rabbits by PET/CT imaging...
December 15, 2016: Autoimmunity Reviews
https://www.readbyqxmd.com/read/27939141/clinical-profile-and-changes-of-serum-lipid-levels-in-epileptic-patients-after-cerebral-infarction
#5
Ken Ikeda, Masahiro Sawada, Harumi Morioka, Maya Kyuzen, Junya Ebina, Junpei Nagasawa, Masaru Yanagihashi, Ken Miura, Yuichi Ishikawa, Takehisa Hirayama, Takanori Takazawa, Osamu Kano, Kiyokazu Kawabe, Yasuo Iwasaki
BACKGROUND: Antiepileptic drugs (AEDs) may increase development of dyslipidemia and cerebrovascular disease (CVD). We examined the clinical profile and changes of serum lipid levels after AED monotherapy in patients with poststroke epilepsy (PSE) after cerebral infarction (CI). SUBJECTS AND METHODS: Medical records were reviewed in consecutive 2144 CI patients. Monotherapy of valproate, carbamazepine (CBZ), phenytoin (PHT), zonisamide, levetiracetam, or lamotrigine was performed in PSE patients...
December 8, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/27932349/nadph-oxidase-2-and-atherothrombosis-insight-from-chronic-granulomatous-disease
#6
REVIEW
Francesco Violi, Roberto Carnevale, Lorenzo Loffredo, Pasquale Pignatelli, John I Gallin
The phagocytic cell enzyme NADPH oxidase-2 (Nox2) is critical for killing micro-organisms via production of reactive oxygen species and thus is a key element of the innate immune system. Nox2 is also detectable in endothelial cells and platelets where it has vasoconstrictive and aggregating properties, respectively. Patients with X-linked chronic granulomatous disease with hereditary Nox2 deficiency not only have impaired bacterial killing but, in association with loss of Nox2 function, also have enhanced carotid artery dilation, impaired platelet-related thrombosis, and reduced carotid atherosclerotic burden...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27892731/is-arachidonic-acid-stimulation-really-a-test-for-the-response-to-aspirin-time-to-think-again
#7
Bartosz Olechowski, Alexander Ashby, Mark Mariathas, Vikram Khanna, Michael Mahmoudi, Nick Curzen
Platelets play a key role in pathogenesis of atherothrombosis. Activated platelets initiate thrombus formation. Antiplatelet therapy (APT) modifies these properties. APT involves aspirin. The existence of 'aspirin resistance' is reported in many populations with cardiovascular disease. The prevalence of this phenomenon is highly variable, affecting more than 50% of patient subgroups in some papers. Areas covered: This review describes the prevalence of 'aspirin resistance', analyses why there is so much apparent variation and addresses whether the commonly used tests of aspirin response are in fact accurately assessing its functional performance...
January 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/27866916/blood-coagulation-in-immunothrombosis-at-the-frontline-of-intravascular-immunity
#8
REVIEW
Florian Gaertner, Steffen Massberg
While hemostasis is the physiological process that prevents blood loss after vessel injury, thrombosis is often portrayed as a pathologic event involving blood coagulation and platelet aggregation eventually leading to vascular occlusion and tissue damage. However, recent work suggests that thrombosis can also be a physiological process, termed immunothrombosis, initiated by the innate immune system providing a first line of defense to locally control infection. Fibrin forms the structural basis of immunothrombotic clots and its assembly involves the concerted action of coagulation factors, platelets and leukocytes...
December 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27830572/inflammation-associated-co-morbidity-between-depression-and-cardiovascular-disease
#9
Angelos Halaris
Morbidity and mortality of cardiovascular disease (CVD) is exceedingly high worldwide. Depressive illness is a serious psychiatric illness that afflicts a significant portion of the world population. Epidemiological studies have confirmed the high co-morbidity between these two disease entities. The co-morbidity is bidirectional and the mechanisms responsible for it are complex and multifaceted. In addition to genetic, biological systems, psychosocial, and behavioral factors that are involved include the central and autonomic nervous systems, the neuroendocrine, immune, and the vascular and hematologic systems...
2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27814786/usefulness-of-mean-platelet-volume-to-predict-significant-coronary-artery-disease-in-patients-with-non-st-elevation-acute-coronary-syndromes
#10
Tuncay Taskesen, Harsimran Sekhon, Igor Wroblewski, Mikhail Goldfarb, Muhammad B Ahmad, Quang T Nguyen, Ibtihaj A M Fughhi, Adi Gidron, Shahriar Dadkhah
Acute coronary syndrome (ACS) is characterized by unstable plaque with thrombotic process involving central role of platelets. The diagnosis and prediction of significant coronary artery disease (CAD) in non-ST-elevation ACS (NSTE-ACS) can be challenging. The central role of platelets in acute atherothrombosis in NSTE-ACS spurred appreciable interest in the diagnostic and predictive role of platelet activity. Mean platelet volume (MPV) is one of the most promising laboratory markers in patients with CAD. This retrospective study was designed to investigate the diagnostic and predictive value of high MPV levels in patients with NSTE-ACS with significant CAD...
January 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/27789143/prognostic-significance-of-atrial-fibrillation-in-lower-limb-amputee-patients
#11
S Ralevic, J Perunicic, R Lasica, J Marinkovic, T Blagojevic, I Simanic, M Asanin, G Stankovic
OBJECTIVE: In patients with risk factors or established atherothrombosis, atrial fibrillation (AF) is associated with a poor prognosis compared with patients without AF. The aim of this study was to evaluate the prevalence of AF in patients with lower limb amputation (LLA) and its association with cardiovascular death and adverse cardiovascular events in long-term follow-up. METHODS: Observational prospective study of consecutive patients after index major (transfemoral and transtibial) LLA...
December 2016: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/27766315/cross-linking-gpvi-fc-by-anti-fc-antibodies-potentiates-its-inhibition-of%C3%A2-atherosclerotic-plaque-and-collagen-induced-platelet-activation
#12
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
https://www.readbyqxmd.com/read/27766047/microrna-in-atherothromobosis-is-it-useful-as-a-disease-marker
#13
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
https://www.readbyqxmd.com/read/27725801/early-effects-of-treatment-low-dose-atorvastatin-on-markers-of-insulin-resistance-and-inflammation-in-patients-with-myocardial-infarction
#14
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
https://www.readbyqxmd.com/read/27720831/imaging-flow-cytometry-in-the-assessment-of-leukocyte-platelet-aggregates
#15
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...
January 1, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27709225/increased-circulating-resistin-is-associated-with-insulin-resistance-oxidative-stress-and-platelet-activation-in-type-2-diabetes-mellitus
#16
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...
November 30, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27694321/inverse-agonism-at-the-p2y12-receptor-and-ent1-transporter-blockade-contribute-to-platelet-inhibition-by-ticagrelor
#17
Riyaad Aungraheeta, Alexandra Conibear, Mark Butler, Eamonn Kelly, Sven Nylander, Andrew Mumford, Stuart J 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 characterize its molecular mechanism of action. Initial studies showed that ticagrelor promoted a greater inhibition of adenosine 5'-diphosphate (ADP)-induced Ca(2+) release in washed platelets vs 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...
December 8, 2016: Blood
https://www.readbyqxmd.com/read/27680665/angina-and-future-cardiovascular-events-in-stable-patients-with-coronary-artery-disease-insights-from-the-reduction-of-atherothrombosis-for-continued-health-reach-registry
#18
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...
September 28, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27648176/study-of-atherogenic-lipid-profile-high-sensitive-c-reactive-protein-neurological-deficit-and-short-term-outcome-in-stroke-subtypes
#19
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
https://www.readbyqxmd.com/read/27631489/differential-expression-of-micrornas-in-endarterectomy-specimens-taken-from-patients-with-asymptomatic-and-symptomatic-carotid-plaques
#20
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
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