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ferric chloride mouse model

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)...
August 25, 2016: 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...
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
Catherine Strassel, Lucia Kubovcakova, Pierre H Mangin, Catherine Ravanat, Monique Freund, Radek C Skoda, Cécile V Denis, Arnaud Dupuis, Raoul Herbrecht, Christian Gachet, François Lanza
We studied haemostasis in two mouse models with thrombocytosis caused by different pathogenic mechanisms. In one strain (Yall;Mpl-/-) thrombocytosis is driven by a misbalance between thrombopoietin and its receptor, whereas in the other strain, thrombocytosis is caused by expressing a human JAK2-V617F transgene (FF1) that depends on activation by Cre-recombinase (VavCre;FF1, MxCre;FF1). Thrombotic responses were increased following some, but not all types of challenges. In a vaso-occlusive thrombotic model following collagen-adrenaline injection we found increased mortality in both strains...
February 2015: Thrombosis and Haemostasis
Zhi-Gang She, Xiangyou Liu, Venkata R Kotamraju, Erkki Ruoslahti
Application of anticoagulants remains the primary strategy for prevention and treatment of thrombosis. However, high rate of bleeding complications limits their use. The peptide anticoagulant bivalirudin has been reported to exhibit a lower rate of bleeding complications than heparin, and it also has the advantage of not causing thrombocytopenia, which is a problem with heparin. Nonetheless, hemorrhage is the most common complication of bivalirudin therapy, and there is no effective antidote. Here we use a thrombus-binding peptide, CR(NMe)EKA, to accomplish selective delivery of the bivalirudin-carrying micellar nanocarrier to sites of thrombosis...
October 28, 2014: ACS Nano
Yasuaki Shida, Natalia Rydz, David Stegner, Christine Brown, Jeffrey Mewburn, Kate Sponagle, Ozge Danisment, Bredon Crawford, Barbara Vidal, Carol A Hegadorn, Cynthia M Pruss, Bernhard Nieswandt, David Lillicrap
Rare missense mutations in the von Willebrand factor (VWF) A3 domain that disrupt collagen binding have been found in patients with a mild bleeding phenotype. However, the analysis of these aberrant VWF-collagen interactions has been limited. Here, we have developed mouse models of collagen-binding mutants and analyzed the function of the A3 domain using comprehensive in vitro and in vivo approaches. Five loss-of-function (p.S1731T, p.W1745C, p.S1783A, p.H1786D, A3 deletion) and 1 gain-of-function (p.L1757A) variants were generated in the mouse VWF complementary DNA...
September 11, 2014: Blood
Sapha Mosawy, Denise E Jackson, Owen L Woodman, Matthew D Linden
Diabetes is associated with increased cardiovascular risk. We have recently shown that the naturally occurring flavonol quercetin (Que) or the synthetic flavonol 3',4'-dihydroxyflavonol (DiOHF) inhibits platelet function and delays thrombus formation in healthy mice. Therefore, the aim of this study was to investigate the effect of Que or DiOHF treatment on platelet function and ferric chloride-induced carotid artery thrombosis in a mouse model of type 1 diabetes. Diabetic mice treated with Que or DiOHF maintained blood flow at a significantly higher level than untreated diabetic mice at the end of the recording period...
May 2014: Diabetes & Vascular Disease Research
Anton Matafonov, Philberta Y Leung, Adam E Gailani, Stephanie L Grach, Cristina Puy, Qiufang Cheng, Mao-Fu Sun, Owen J T McCarty, Erik I Tucker, Hiroaki Kataoka, Thomas Renné, James H Morrissey, Andras Gruber, David Gailani
The plasma zymogens factor XII (fXII) and factor XI (fXI) contribute to thrombosis in a variety of mouse models. These proteins serve a limited role in hemostasis, suggesting that antithrombotic therapies targeting them may be associated with low bleeding risks. Although there is substantial epidemiologic evidence supporting a role for fXI in human thrombosis, the situation is not as clear for fXII. We generated monoclonal antibodies (9A2 and 15H8) against the human fXII heavy chain that interfere with fXII conversion to the protease factor XIIa (fXIIa)...
March 13, 2014: Blood
Thilo Witsch, Maximilian Mauler, Nadine Herr, Daniela Stallmann, Christoph Bode, Christoph Hehrlein, Daniel Duerschmied
We tested the feasibility of local thrombolytic therapy via a novel hollow flexible and perforated wire in a mouse model of deep vein thrombosis. Inferior vena cava (IVC) thrombosis was induced by vessel wall exposure to ferric chloride after laparotomy in anesthetized C57Bl/6 mice. Thrombus formation was visualized by intravital microscopy of rhodamine-labeled platelets and leukocytes. A nitinol hypotube coronary wire with perforated tip was inserted via a 0.8 × 40 mm canula into the IVC lumen distal to the site of ferric chloride exposure...
May 2014: Journal of Thrombosis and Thrombolysis
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