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An optimized murine model of ferric chloride-induced arterial thrombosis for thrombosis research

Published on Jan 1, 2005in Thrombosis Research 3.27
· DOI :10.1016/j.thromres.2004.07.009
Xinkang Wang13
Estimated H-index: 13
(BMS: Bristol-Myers Squibb),
Lin Xu1
Estimated H-index: 1
(BMS: Bristol-Myers Squibb)
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Abstract
Abstract Introduction/Objectives Animal models are important tools in thrombosis research and preclinical drug development. Ferric chloride has been widely used to induce arterial thrombosis in a variety of species. However, almost all previous reports applied a very high concentration of ferric chloride (10–60%) to induce thrombus formation leading to difficulties in evaluating the efficacy of antithrombotic agents. Thus, the purpose of this study was to refine the ferric-chloride-induced thrombosis model to be better suited for thrombosis research. Methods and results Dose-dependent study was used to identify a threshold concentration of ferric chloride sufficient for consistent occlusion (as reflected by the Doppler blood flow) of the carotid artery in C57BL/6 mice. Ferric chloride concentration at or about a threshold of 2.5% was found to be sensitive to anticoagulant (e.g., heparin) and antiplatelet (e.g., clopidogrel) agents. In contrast, the vessel rapidly occluded at or above 5% ferric chloride concentration despite pretreatment with the antithrombotic agents, even at doses that exerted maximal prolongation of tail bleeding time. Conclusions Our study provides a simple, sensitive and highly controlled method for limiting vessel injury in mice to better detect the efficacy of antithrombotic drugs and/or evaluate therapeutic targets.
  • References (8)
  • Citations (97)
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References8
Newest
Published on Aug 15, 2001in Blood 16.56
Susan S. Smyth20
Estimated H-index: 20
,
Ernane D. Reis19
Estimated H-index: 19
+ 2 AuthorsBarry S. Coller44
Estimated H-index: 44
Platelet integrin αIIbβ3 (GPIIb/IIIa) plays a central role in the initiation of arterial thrombosis, but its contribution to disseminated microvascular thrombosis is less well defined. Therefore, wild-type mice (β3+/+), β3-integrin–deficient mice (β3−/−), and wild-type mice treated with a hamster monoclonal antibody (1B5) that blocks murine αIIbβ3 function were tested in models of large-vessel and microvascular thrombosis. In the large-vessel model, ferric chloride was used to injure the carotid...
Published on Jan 30, 2001in Circulation 23.05
Stavros Konstantinides5
Estimated H-index: 5
(Scripps Research Institute),
Katrin Schäfer21
Estimated H-index: 21
(Scripps Research Institute)
+ 1 AuthorsDavid J. Loskutoff80
Estimated H-index: 80
(Scripps Research Institute)
Background—The origin and contribution of plasminogen activator inhibitor-1 (PAI-1) and its cofactor vitronectin (VN) to arterial thrombosis/thrombolysis in vivo is controversial. Methods and Results—Ferric chloride was used to induce carotid artery injury in 97 wild-type (WT), 84 PAI-1−/−, and 84 VN−/− mice. Complete thrombotic occlusion was observed in 70% of PAI-1−/− mice versus 92% of WT (P<0.001) and 87% of VN−/− (P=0.015) mice. In vessels that occluded, mean times to occlusion were signifi...
Robert J. Leadley2
Estimated H-index: 2
(Pfizer),
Liguo Chi1
Estimated H-index: 1
(Pfizer)
+ 1 AuthorsAlison W. Gagnon3
Estimated H-index: 3
(Aventis Pharma)
Abstract Cardiovascular and cerebrovascular diseases continue to be the leading cause of death throughout the world. Over the past two decades, great advances have been made in the pharmacological treatment and prevention of thrombotic disorders (e.g., tissue plasminogen activators, platelet GPIIb/IIIa antagonists, ADP receptor antagonists such as clopidogrel, low-molecular weight heparins, and direct thrombin inhibitors). New research is leading to the next generation of antithrombotic compound...
Published on Jun 15, 1999in Circulation 23.05
Yanhong Zhu5
Estimated H-index: 5
(UM: University of Michigan),
Peter Carmeliet1
Estimated H-index: 1
(UM: University of Michigan),
William P. Fay33
Estimated H-index: 33
(UM: University of Michigan)
Background—Platelet-rich thrombi are resistant to lysis by tissue plasminogen activator (tPA). Plasminogen activator inhibitor-1 (PAI-1), a rapid inhibitor of tPA, may contribute to arterial thrombolysis resistance. However, few data are available regarding the effect of PAI-1 on arterial thrombolysis in animals. We used a murine carotid injury model to test the hypothesis that PAI-1 inhibits thrombolysis mediated by pharmacological concentrations of tPA. Methods and Results—Platelet-rich thromb...
Published on Mar 1, 1997in Blood Coagulation & Fibrinolysis 1.12
David Gailani40
Estimated H-index: 40
,
Nina Lasky9
Estimated H-index: 9
,
George J. Broze55
Estimated H-index: 55
To facilitate investigations into the physiologic and pathologic roles of factor XI, we have developed a murine model of severe factor XI deficiency using the technique of homologous recombination in embryonic stem cells. The factor XI gene was disrupted by introducing a neomycin phosphotransferase
Published on Aug 12, 1996in JAMA Internal Medicine 20.77
Robert Raschke17
Estimated H-index: 17
,
Bea Gollihare2
Estimated H-index: 2
,
John C. Peirce1
Estimated H-index: 1
Objective: To determine the effectiveness of the nomogram in a community hospital that implemented it as a practice guideline. Design: A nonexperimental, retrospective time series. Setting: A 600-bed community teaching hospital and regional referral center in Phoenix, Ariz. Patients: The study population included 591 consecutive patients with venous thromboembolism, treated over a 5-year study period. Methods: During this period, the weight-based heparin nomogram was adapted into a preprinted or...
Published on Jan 1, 1996in The Lancet 59.10
David Bergqvist71
Estimated H-index: 71
Background Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. Methods CAPRIE was a randomised, blinded, international trial designed to assess the relative effic...
Published on Nov 1, 1990in Thrombosis Research 3.27
Kenneth D. Kurz4
Estimated H-index: 4
,
B. W. Main1
Estimated H-index: 1
,
George Sandusky1
Estimated H-index: 1
Abstract The purposes of these studies were to produce a small animal model of arterial thrombosis for study of novel antithrombotic agents, to validate a simple temperature index of occlusive thrombosis, and to describe the composition of the thrombus. Small thermocouple transducers were fabricated from readily available materials. A thermocouple was inserted under a carotid artery of the anesthetized rat and vessel temperature was recorded continuously. Arterial injury was induced by FeC1 3 so...
Cited By97
Newest
Published on Jul 24, 2019in Journal of Biophotonics 3.76
Yao Yu1
Estimated H-index: 1
,
Menghan Yu + 5 AuthorsZhenhe Ma5
Estimated H-index: 5
Published on Apr 1, 2019in Thrombosis and Haemostasis 4.73
Maithili Sashindranath10
Estimated H-index: 10
(Monash University),
Sharelle A. Sturgeon12
Estimated H-index: 12
(Monash University)
+ 8 AuthorsJustin Raymond Hamilton20
Estimated H-index: 20
(Monash University)
Background: Arterial thrombosis models are important for preclinical evaluation of antithrombotics but how anesthetic protocol can influence experimental results is not studied. Objectives: We studied how three most commonly used rodent anesthetics affect the induction of thrombosis and thrombus resolution with antiplatelet agent integrilin (Eptifibatide). Methods: The Folts, electrolytic, and FeCl3 models of carotid artery thrombosis were evaluated. The extent of blood flow reduction required t...
Published on Apr 1, 2019in Cytotherapy 4.30
Giane Daniela Carneiro3
Estimated H-index: 3
(State University of Campinas),
Micheli S. Sielski2
Estimated H-index: 2
(State University of Campinas)
+ 3 AuthorsCristina P. Vicente11
Estimated H-index: 11
(State University of Campinas)
Abstract Background Endothelial progenitor cells (EPCs) are circulating progenitor cells that can play an essential role in vascular remodelling. In this work, we compared the role of two EPCs cultivated with different mediums in the resolution of the arterial thrombus induced by FeCl 3 lesion and in vessel re-endothelization in the mouse carotid artery. Methods Mice mononuclear cells were differentiated into EPCs using Dulbecco's Modified Eagle's Medium (DMEM) and vascular endothelial growth fa...
Published on Dec 1, 2018in Scientific Reports 4.01
Rena Kasimu5
Estimated H-index: 5
(XMU: Xinjiang Medical University),
Xinling Wang1
Estimated H-index: 1
(XMU: Xinjiang Medical University)
+ 3 AuthorsYuming Mu (First Affiliated Hospital of Xinjiang Medical University)
Salvia deserta Schang (SDS) belongs to the same family as Salvia miltiorrhiza bunge, one of the antithrombotic Chinese herbal medicines. In our study, EtOAc root extracts were analyzed for their effects on adenosine diphosphate (ADP)-induced platelet aggregation in rabbits and FeCl3-induced rat common carotid artery thrombosis as well as on rat blood plasma concentrations of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1α), antithrombin-III (AT-III), protein C (PC), plasminoge...
Published on Sep 1, 2018in Journal of Stroke & Cerebrovascular Diseases 1.65
Ulises Gómez-Pinedo14
Estimated H-index: 14
(CSIC: Spanish National Research Council),
Leyre Sanchez-Rojas1
Estimated H-index: 1
(CSIC: Spanish National Research Council)
+ 10 AuthorsMaite del Olmo4
Estimated H-index: 4
Introduction Stroke represents an attractive target for cell therapy. Although different types of cells have been employed in animal models with variable results, the human adipose-derived stem cells (hASCs) have demonstrated favorable characteristics in the treatment of diseases with inflammatory substrate, but experience in their intracerebral administration is lacking. The purpose of this study is to evaluate the effect and safety of the intracerebral application of hASCs in a stroke model. M...
Published on Aug 9, 2018in JCI insight
Donny Hanjaya-Putra10
Estimated H-index: 10
,
Carolyn A. Haller19
Estimated H-index: 19
+ 10 AuthorsThomas Bonnard4
Estimated H-index: 4
Published on Jan 2, 2018in PLOS ONE 2.78
Julia Novotny2
Estimated H-index: 2
,
Sue Chandraratne7
Estimated H-index: 7
+ 16 AuthorsAnna Titova3
Estimated H-index: 3
Medical treatment of arterial thrombosis is mainly directed against platelets and coagulation factors, and can lead to bleeding complications. Novel antithrombotic therapies targeting immune cells and neutrophil extracellular traps (NETs) are currently being investigated in animals. We addressed whether immune cell composition of arterial thrombi induced in mouse models of thrombosis resemble those of human patients with acute myocardial infarction (AMI).In a prospective cohort study of patients...
Published on Dec 1, 2017in Scientific Reports 4.01
F Günther (University of Freiburg), Timo Heidt4
Estimated H-index: 4
(University of Freiburg)
+ 12 AuthorsAndreas Zirlik22
Estimated H-index: 22
(University of Freiburg)
Platelets can be found on the surface of inflamed and ruptured atherosclerotic plaques. Thus, targeting of activated platelets may allow for molecular imaging of vulnerable atherosclerotic lesions. We here investigated microbubbles (MB) functionalized with the selectin ligand sialyl Lewisa individually (MBsLea) or dually with sLea and an antibody targeting ligand-induced binding sites of the activated GPIIb/IIIa receptor (MBDual). Assessed by in vitro flow chamber, targeted MB exhibited increase...
Published on Nov 28, 2017in Science Signaling 6.48
Sarah Nicol Lauder13
Estimated H-index: 13
(Cardiff University),
Keith Allen-Redpath3
Estimated H-index: 3
(Cardiff University)
+ 24 AuthorsVictoria J. Tyrrell5
Estimated H-index: 5
(Cardiff University)
Blood coagulation functions as part of the innate immune system by preventing bacterial invasion, and it is critical to stopping blood loss (hemostasis). Coagulation involves the external membrane surface of activated platelets and leukocytes. Using lipidomic, genetic, biochemical, and mathematical modeling approaches, we found that enzymatically oxidized phospholipids (eoxPLs) generated by the activity of leukocyte or platelet lipoxygenases (LOXs) were required for normal hemostasis and promote...
Published on Jul 21, 2017in Frontiers in Pharmacology 3.85
Bo Yu9
Estimated H-index: 9
(Liaoning Normal University),
Guangping Zhang2
Estimated H-index: 2
+ 5 AuthorsTonghui Ma48
Estimated H-index: 48
(Dalian Medical University)
Traditional Chinese medicine has been used to treat a variety of human diseases for many centuries. Zanthoxylum nitidum var. tomentosum is used as an adjuvant to promote blood circulation and remove stasis. However, the mechanisms of improving circulation and other biological activities of Z. nitidum var. tomentosum are still unclear. Plasminogen activator inhibitor-1 (PAI-1) regulates the plasminogen activation system through inhibition of tissue-type and urokinase-type plasminogen activators (...