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ferric chloride mouse model

Mikel Allende, Eva Molina, Ramón Lecumberri, Juan Antonio Sanchez-Arias, Ana Ugarte, Elizabeth Guruceaga, Julen Oyarzabal, José Hermida
Antithrombotic medications target coagulation factors. Their use is associated with an increased bleeding risk. Safer drugs are needed. The heat shock protein 70 (Hsp70) exhibits antithrombotic properties that do not influence bleeding. By using murine models, we aimed to test the hypothesis that overexpressing Hsp70 with CM-695, a first in class dual inhibitor of HDAC6 and phosphodiesterase 9, protects against thrombosis while leaves bleeding tendency unaltered. CM-695 was used to induce Hsp70 overexpression...
August 30, 2017: Thrombosis and Haemostasis
Heidrun Degen, Oliver Borst, Melanie Ziegler, Ann-Katrin Mojica Munoz, Janina Jamasbi, Britta Walker, Silvia Göbel, Julia Fassbender, Kristin Adler, Richard Brandl, Götz Münch, Reinhard Lorenz, Wolfgang Siess, Meinrad Gawaz, Martin Ungerer
BACKGROUND: GPVI (Glycoprotein VI) is the essential platelet collagen receptor in atherothrombosis. Dimeric GPVI-Fc (Revacept) binds to GPVI binding sites on plaque collagen. As expected, it did not increase bleeding in clinical studies. GPVI-Fc is a potent inhibitor of atherosclerotic plaque-induced platelet aggregation at high shear flow, but its inhibition at low shear flow is limited. We sought to increase the platelet inhibitory potential by fusing GPVI-Fc to the ectonucleotidase CD39 (fusion protein GPVI-CD39), which inhibits local ADP accumulation at vascular plaques, and thus to create a lesion-directed dual antiplatelet therapy that is expected to lack systemic bleeding risks...
July 27, 2017: Journal of the American Heart Association
Bing Li, Cong Fu, Genshan Ma, Quli Fan, Yuyu Yao
Thrombosis is a main cause of acute cardiovascular events, and detecting thrombi in small arteries via noninvasive imaging remains challenging. In this study, we employed a novel imaging method, photoacoustic imaging (PAI), to study thrombosis in a mouse model of ferric chloride (FeCl3)-induced arterial thrombosis and compared the ability of this method to detect thrombosis with that of a conventional imaging method, namely, ultrasound. The mice (n = 20) were divided equally into the following 4 groups: (1) a normal group, and (2) 3 experimental groups, in which the left common carotid artery was treated with 20% FeCl3 for 1, 3, or 5 min, respectively...
2017: Journal of Vascular Research
Yuanyuan Zhang, Long Li, Yazheng Zhao, Han Han, Yang Hu, Di Liang, Boyang Yu, Junping Kou
Arterial thrombosis and its related diseases are major healthcare problems worldwide. Blebbistatin is an inhibitor of myosin II, which plays an important role in thrombosis. The aim of our study is to explore the effect and potential mechanism of blebbistatin on arterial thrombosis. A ferric chloride (FeCl3 ) solution at a concentration of 5% was used to induce carotid artery thrombosis in mice. Immunohistochemistry and immunofluorescence staining were used to detect the expression or activation of non-muscle myosin heavy chain IIA (NMMHC IIA), tissue factor (TF), GSK3β and NF-κB...
2017: International Journal of Biological Sciences
Sara Martinez de Lizarrondo, Clément Gakuba, Bradley A Herbig, Yohann Repessé, Carine Ali, Cécile V Denis, Peter J Lenting, Emmanuel Touzé, Scott L Diamond, Denis Vivien, Maxime Gauberti
BACKGROUND: Platelet cross-linking during arterial thrombosis involves von Willebrand Factor (VWF) multimers. Therefore, proteolysis of VWF appears promising to disaggregate platelet-rich thrombi and restore vessel patency in acute thrombotic disorders such as ischemic stroke, acute coronary syndrome, or acute limb ischemia. N -Acetylcysteine (NAC, a clinically approved mucolytic drug) can reduce intrachain disulfide bonds in large polymeric proteins. In the present study, we postulated that NAC might cleave the VWF multimers inside occlusive thrombi, thereby leading to their dissolution and arterial recanalization...
August 15, 2017: Circulation
Changsun Kang, Sian Gwon, ChulGyu Song, Peter M Kang, Seong-Cheol Park, Jongho Jeon, Do Won Hwang, Dongwon Lee
A thrombus (blood clot) is formed in injured vessels to maintain the integrity of vasculature. However, obstruction of blood vessels by thrombosis slows blood flow, leading to death of tissues fed by the artery and is the main culprit of various life-threatening cardiovascular diseases. Herein, we report a rationally designed nanomedicine that could specifically image obstructed vessels and inhibit thrombus formation. On the basis of the physicochemical and biological characteristics of thrombi such as an abundance of fibrin and an elevated level of hydrogen peroxide (H2O2), we developed a fibrin-targeted imaging and antithrombotic nanomedicine, termed FTIAN, as a theranostic system for obstructive thrombosis...
June 27, 2017: ACS Nano
Jocelyn M Choo, Jackie K Cheung, Jessica A Wisniewski, David L Steer, Dieter M Bulach, Thomas J Hiscox, Anjana Chakravorty, A Ian Smith, David A Gell, Julian I Rood, Milena M Awad
The ability of a pathogenic bacterium to scavenge iron from its host is important for its growth and survival during an infection. Our studies on C. perfringens gas gangrene strain JIR325, a derivative of strain 13, showed that it is capable of utilizing both human hemoglobin and ferric chloride, but not human holo-transferrin, as an iron source for in vitro growth. Analysis of the C. perfringens strain 13 genome sequence identified a putative heme acquisition system encoded by an iron-regulated surface gene region that we have named the Cht (Clostridium perfringens heme transport) locus...
2016: PloS One
Maarten Criel, Benedetta Izzi, Christophe Vandenbriele, Laurens Liesenborghs, Soetkin Van Kerckhoven, Marleen Lox, Katrien Cludts, Elizabeth A V Jones, Thomas Vanassche, Peter Verhamme, Marc Hoylaerts
BACKGROUND: Platelet Endothelial Aggregation Receptor-1 (PEAR1) is a transmembrane platelet receptor that amplifies the activation of the platelet fibrinogen receptor (αIIbβ3) during platelet aggregation. In man, Pear1 polymorphisms are associated with changes in platelet aggregability. In this report, we characterized Pear1 expression and function in murine platelets. METHODS: Pear1 phosphorylation and signaling, platelet aggregation, α-degranulation and clot retraction were studied in WT and Pear1(-/-) platelets...
October 2016: Thrombosis Research
Yizhu Chen, Wenlong Yang, Lingyu Guo, Xiaolin Wu, Tiantian Zhang, Junling Liu, Junfeng Zhang
Platelets play a crucial role in the development and progression of atherosclerosis-thrombosis and, therefore, antiplatelet drugs are widely used in the treatment of coronary artery disease. Moreover, advances in understanding the biological functions of natural plant products can provide new pharmacological strategies aimed at promoting cardiovascular health. Atractylenolide I (ATL-1), ATL-2, and ATL-3 are the major bioactive components of a Qi tonifying medicinal herb Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala), which is commonly used in traditional Chinese medicine (TCM)...
March 2017: Platelets
Ziane Elaïb, Frédéric Adam, Eliane Berrou, Jean-Claude Bordet, Nicolas Prévost, Régis Bobe, Marijke Bryckaert, Jean-Philippe Rosa
The role of the sarco-endoplasmic reticulum calcium (Ca(2+)) adenosine triphosphatase (ATPase) 3 (SERCA3) in platelet physiology remains poorly understood. Here, we show that SERCA3 knockout (SERCA3(-/-)) mice exhibit prolonged tail bleeding time and rebleeding. Thrombus formation was delayed both in arteries and venules in an in vivo ferric chloride-induced thrombosis model. Defective platelet adhesion and thrombus growth over collagen was confirmed in vitro. Adenosine 5'-diphosphate (ADP) removal by apyrase diminished adhesion and thrombus growth of control platelets to the level of SERCA3(-/-) platelets...
August 25, 2016: Blood
Xiaowei Wang, Yannik Gkanatsas, Jathushan Palasubramaniam, Jan David Hohmann, Yung Chih Chen, Bock Lim, Christoph E Hagemeyer, Karlheinz Peter
RATIONALE: Myocardial infarction and stroke are leading causes of morbidity/mortality. The typical underlying pathology is the formation of thrombi/emboli and subsequent vessel occlusion. Systemically administered fibrinolytic drugs are the most effective pharmacological therapy. However, bleeding complications are relatively common and this risk as such limits their broader use. Furthermore, a rapid non-invasive imaging technology is not available. Thereby, many thrombotic events are missed or only diagnosed when ischemic damage has already occurred...
2016: Theranostics
Kousaku Ohno, Atsuyuki Tomizawa, Joseph A Jakubowski, Makoto Mizuno, Atsuhiro Sugidachi
The present study examined the effects of prasugrel in a mouse model of thrombosis-induced neointimal hyperplasia. Following carotid artery injury by application of ferric chloride solution, thrombus formation was assessed on Day 1 and neointimal thickening was assessed on Day 21. Single administrations of prasugrel at 0.3-3mg/kg (p.o.) resulted in a dose-related and sustained inhibition of ADP-induced platelet aggregation through 24h. Single and multiple (1 and 3 weeks) administration of prasugrel (3mg/kg loading and 1mg/kg/day maintenance doses) resulted in a marked inhibition of neointimal thickening in the injured artery...
December 2015: Thrombosis Research
Satish B Cheepala, Aaron Pitre, Yu Fukuda, Kazumasa Takenaka, Yuanyuan Zhang, Yao Wang, Sharon Frase, Tamara Pestina, T Kent Gartner, Carl Jackson, John D Schuetz
Controlling the activation of platelets is a key strategy to mitigate cardiovascular disease. Previous studies have suggested that the ATP-binding cassette (ABC) transporter, ABCC4, functions in platelet-dense granules. Using plasma membrane biotinylation and super-resolution microscopy, we demonstrate that ABCC4 is primarily expressed on the plasma membrane of both mouse and human platelets. Platelets lacking ABCC4 have unchanged dense-granule function, number, and volume, but harbor a selective impairment in collagen-induced aggregation...
November 12, 2015: Blood
Thomas Bonnard, Christoph E Hagemeyer
Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric chloride injury is now a well-established technique to rapidly and accurately induce the formation of thrombi in exposed veins or artery of small and large diameter. This model has played a key role in the study of the pathophysiology of thrombosis, in the discovery and validation of novel antithrombotic drugs and in the understanding of the mechanism of action of these new agents...
June 29, 2015: Journal of Visualized Experiments: JoVE
Ming-Lu Liang, Xing-Wen Da, Ao-Di He, Guang-Qiang Yao, Wen Xie, Gang Liu, Ji-Zhou Xiang, Zhang-Yin Ming
Flavonoids exert both anti-oxidant and anti-platelet activities in vitro and in vivo. Pentamethylquercetin (PMQ), a polymethoxylated flavone derivative, has been screened for anti-carcinogenic and cardioprotective effects. However, it is unclear whether PMQ has anti-thrombotic effects. In the present study, PMQ (20 mg/kg) significantly inhibited thrombus formation in the collagen- epinephrine- induced acute pulmonary thrombosis mouse model and the ferric chloride-induced carotid injury model. To explore the mechanism, we evaluated the effects of PMQ on platelet function...
2015: Scientific Reports
Brian C Cooley
BACKGROUND: The mechanism of thrombotic induction in experimental models can vary greatly, as can the applied evaluative measures, making comparisons among models difficult. OBJECTIVES: This study comparatively evaluated the arterial thrombodynamic response among injury mechanisms. METHODS: Thrombotic responses were induced in mouse carotid arteries, with subsequent intravital imaging using rhodamine-6G-labeled platelets to quantitate platelet accumulation over 30minutes...
May 2015: Thrombosis Research
Hong Jin, Milena A Gebska, Ilya O Blokhin, Katina M Wilson, Pimonrat Ketsawatsomkron, Anil K Chauhan, Henry L Keen, Curt D Sigmund, Steven R Lentz
OBJECTIVE: We tested the hypothesis that endothelial peroxisome proliferator-activated receptor-γ protects against vascular thrombosis using a transgenic mouse model expressing a peroxisome proliferator-activated receptor-γ mutant (E-V290M) selectively in endothelium. APPROACH AND RESULTS: The time to occlusive thrombosis of the carotid artery was significantly shortened in E-V290M mice compared with nontransgenic littermates after either chemical injury with ferric chloride (5...
April 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
Jun-Hui Choi, Seung Kim, Sung-Jun Kim
We investigated in vitro and in vivo fibrinolytic and antithrombotic activity of spirulan and analyzed its partial biochemical properties. Spirulan, a sulfated polysaccharide from the blue-green alga Arthrospira platensis, exhibits antithrombotic potency. Spirulan showed a strong fibrin zymogram lysis band corresponding to its molecular mass. It specifically cleaved Aα and Bβ, the major chains of fibrinogen. Spirulan directly decreased the activity of thrombin and factor X activated (FXa), procoagulant proteins...
May 2015: Journal of Biochemical and Molecular Toxicology
Vasile I Pavlov, Ying S Tan, Erin E McClure, Laura R La Bonte, Chenhui Zou, William B Gorsuch, Gregory L Stahl
Myocardial infarction and coagulation disorders are leading causes of disability and death in the world. An important role of the lectin complement pathway in myocardial infarction and coagulation has been demonstrated in mice genetically deficient in lectin complement pathway proteins. However, these studies are limited to comparisons between wild-type and deficient mice and lack the ability to examine reversal/inhibition of injury after disease establishment. We developed a novel mouse that expresses functional human mannose-binding lectin (MBL) 2 under the control of Mbl1 promoter...
February 2015: American Journal of Pathology
W P Sheffield, L J Eltringham-Smith, S Gataiance, V Bhakta
The leech protein hirudin is a potent natural thrombin inhibitor. Its potential as an antithrombotic agent is limited by its promotion of bleeding. We attempted to modify this profile by positioning albumin and a plasmin cleavage site on its N-terminus, in recombinant protein HSACHV3 [comprising hirudin variant 3 (HV3) fused to the C-terminus of human serum albumin (HSA) via a plasmin cleavage site (C)], Previously we showed that HSACHV3 inhibited thrombin in a plasmin-dependent manner, and that, unlike HV3, it did not increase bleeding in vivo when administered to mice...
May 2015: Journal of Thrombosis and Thrombolysis
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