Name: a murine model of arterial restenosis: technical aspects of femoral wire injury
Uploaded: 2015-03-10T15:00:00
Description: Watch this Scientific Journal Video about A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury at JoVE.com

This work was supported by a Wisconsin Partnership Program New Investigator Award (ID 2832), a National Heart, Lung, Blood Institute R01 Grant (HL-068673) and a T32 training Grant (HL-110853). We thank Dr. Melina Kibbe&#8217;s group at Northwestern University for providing helpful information.

Declaração de Ética: NOTA: Todos os procedimentos estão em conformidade com o Manual sobre Cuidados e Uso de Animais de Laboratório (National Academies Press, 8ª edição, 2011), e os protocolos aprovados pelo Comitê de Uso e Cuidado Animal Institucional da Universidade de Wisconsin. Todas as cirurgias foram realizadas sob anestesia isoflurano (através de inalação, taxa de fluxo de 2 ml / min), e foram feitos todos os esforços para minimizar o sofrimento. Os animais foram sacrificados numa câmara gradualment...

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	<li>Dzau, V. J., Braun-Dullaeus, R. C., Sedding, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vascular+proliferation+and+atherosclerosis:+new+perspectives+and+therapeutic+strategies.">Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies.</a> Nat Med. 8 (11), 1249-1256 (2002).</li><li>Hui, D. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intimal+hyperplasia+in+murine+models.">Intimal hyperplasia in murine models.</a> Curr Drug Targets. 9 (3), 251-260 (2008).</li><li>Ferns, G. A., Avades, T. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+mechanisms+of+coronary+restenosis:+insights+from+experimental+models.">The mechanisms of coronary restenosis: insights from experimental models.</a> Int J Exp Pathol. 81 (2), 63-88 (2000).</li><li>Sata, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+mouse+model+of+vascular+injury+that+induces+rapid+onset+of+medial+cell+apoptosis+followed+by+reproducible+neointimal+hyperplasia.">A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia.</a> J Mol Cell Cardiol. 32 (11), 2097-2104 (2000).</li><li>Xu, Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+models+of+arteriosclerosis:+from+arterial+injuries+to+vascular+grafts.">Mouse models of arteriosclerosis: from arterial injuries to vascular grafts.</a> Am J Pathol. 165 (1), 1-10 (2004).</li><li>Lv, L., Meng, Q., Ye, M., Wang, P., Xue, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=STAT4+deficiency+protects+against+neointima+formation+following+arterial+injury+in+mice.">STAT4 deficiency protects against neointima formation following arterial injury in mice.</a> J Mol Cell Cardiol. 74C, 284-294 (2014).</li><li>Zhu, B., Kuhel, D. G., Witte, D. P., Hui, D. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Apolipoprotein+E+inhibits+neointimal+hyperplasia+after+arterial+injury+in+mice.">Apolipoprotein E inhibits neointimal hyperplasia after arterial injury in mice.</a> Am J Pathol. 157 (6), 1839-1848 (2000).</li><li>Fu, Y., Duru, E. A., Davies, M. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+metabolic+syndrome+on+the+response+to+arterial+injury.">Effect of metabolic syndrome on the response to arterial injury.</a> J Surg Res. , (2014).</li><li>Kuhel, D. G., Zhu, B., Witte, D. P., Hui, D. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinction+in+genetic+determinants+for+injury-induced+neointimal+hyperplasia+and+diet-induced+atherosclerosis+in+inbred+mice.">Distinction in genetic determinants for injury-induced neointimal hyperplasia and diet-induced atherosclerosis in inbred mice.</a> Arterioscler Thromb Vasc Biol. 22 (6), 955-960 (2002).</li><li>Cooley, B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+strain+differential+neointimal+response+in+vein+grafts+and+wire-injured+arteries.">Mouse strain differential neointimal response in vein grafts and wire-injured arteries.</a> Circ J. 71 (10), 1649-1652 (2007).</li><li>Ishigami, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deficiency+of+CuZn+superoxide+dismutase+promotes+inflammation+and+alters+medial+structure+following+vascular+injury.">Deficiency of CuZn superoxide dismutase promotes inflammation and alters medial structure following vascular injury.</a> J Atheroscler Thromb. 18 (11), 1009-1017 (2011).</li></ol>

O procedimento de lesão fio é aplicável a todas as linhagens de camundongos, desde que as suas estruturas anatômicas são semelhantes. 4 Neste trabalho, utilizou-se do sexo masculino camundongos C57BL / 6 com uma idade de 12-16 semanas. Como aprendemos a partir de nossos estudos preliminares, as artérias femorais de ratos mais jovens de 10 semanas são muitas vezes tão pequeno que a inserção do fio é bastante desafiador. Por outro lado, a inserção do fio nos ratos mais velhos que 16 semanas, é tec...

In the era of expanded application of endovascular treatments for various cardiovascular diseases, restenosis after angioplasty is one of the major problems for patients undergoing such treatments. Damage to the vascular endothelium at the time of angioplasty, in concert with the atherosclerotic background, induces excessive smooth muscle cell proliferation in the medial layer, resulting in neointimal hyperplasia.1,2 A viable animal model that recapitulates post-angioplasty neointimal hyperplasia is, thus, important not only for the investigation of disease mechanisms but also for the development of effective therapeutics to treat this pathology.
Mice represent an excellent model animal to recapitulate neointimal hyperplasia for the following reasons: the genetic backgrounds of experimental mice are well established; a wide variety of genetically-modified strains are available;2 obtaining littermates of the same background is easy; and the cost of the animals is relatively low. Arterial ligation model and wire injury model are the two most common mouse models of mechanically-induced neointimal hyperplasia. The arterial ligation model is easy to create, but physiologically dissimilar to the actual angioplasty procedure. The wire injury model closely mimics actual angioplasty procedures but is technically difficult due to the small size of mouse arteries.2,3 Sata et al. first described a wire injury method for mouse femoral arteries based on the anatomical structure of the vasculature and the use of proper-sized flexible wire. Utilizing this technique, they succeeded in reproducibly inducing neointimal hyperplasia in various strains of mice.4
Although femoral wire injury is a well-established model, some of the technical aspects of the technique are highly challenging compared to other models such as ligation.5 The purpose of this paper is to describe our mouse wire injury model procedures in detail, which is a modified version of Sata&#8217;s original method. We have made two main modifications: 1) Looping only the arteries, and 2) No lidocaine use.

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a murine model of arterial restenosis: technical aspects of femoral wire injury

A doença cardiovascular causadas por aterosclerose é a principal causa de morte no mundo desenvolvido. O estreitamento da luz do vaso, devido ao desenvolvimento da placa aterosclerótica ou a ruptura de placas estabelecidos, interrompe o fluxo normal do sangue levando a várias morbidades, tais como infarto do miocárdio e acidente vascular cerebral. Na clínica procedimentos endovasculares, como a angioplastia são comumente realizados para reabrir o lúmen. No entanto, estes tratamentos inevitavelmente danificar a parede do vaso, bem como o endotélio vascular, desencadeando uma resposta de cicatrização excessiva e o desenvolvimento de uma placa que se estende da neointima no lúmen fazendo com que a restenose do vaso (re-estreitamento). A reestenose permanece uma das principais causas do fracasso dos tratamentos endovasculares para aterosclerose. Assim, os modelos animais pré-clínicos de reestenose são de vital importância para a investigação dos mecanismos fisiopatológicos, bem como translacional abordagens para intervenções vasculares. Entre vários experime murinomodelos ntal, lesão fio artéria femoral é amplamente aceito como o mais adequado para estudos de reestenose pós-angioplastia, pois se assemelha ao procedimento de angioplastia que prejudica a ambos endotélio e da parede do vaso. No entanto, muitos pesquisadores têm dificuldade em utilizar este modelo devido ao seu alto grau de dificuldade técnica. Isto é primeiramente porque um fio de metal tem de ser inserido dentro da artéria femoral, o que é cerca de três vezes mais fino do que o fio, para gerar suficiente para induzir lesão neoíntima proeminente. Aqui, descrevemos os detalhes cirúrgicos essenciais para efetivamente superar as maiores dificuldades técnicas deste modelo. Seguindo os procedimentos apresentados, realizando a lesão de arame artéria femoral de rato torna-se mais fácil. Uma vez familiarizado, todo o processo pode ser concluído no prazo de 20 min.

Quatro semanas após a cirurgia, dissecção da artéria femoral feridos fios e fazer espécime Bloco A parafina para analisar a formação neointima. Induzir anestesia geral, tal como descrito acima. Abra o peito imediatamente e insira uma de calibre 20 borboleta agulha para o ventrículo esquerdo. Ligue a linha para um frasco de infusão. Realizam a fixação de perfusão através de infusão de gotas de PBS, seguido por paraformaldeído a 4% (geralmente 10-20 mL, cada um). O frasco de infusão é colocado ce...

Watch this Scientific Journal Video about A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury at JoVE.com

A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury

O mouse modelo de lesão fio artéria femoral de reestenose é tecnicamente desafiador. Neste protocolo, mostrar os principais detalhes técnicos essencial para a realização com êxito lesão fio para induzir neoï¿½tima consistente para estudos de reestenose.

Um modelo murino de Arterial Restenosis: Aspectos Técnicos do Femoral Injury Fio

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