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.

BEMÆRK: Etik Statement: Alle procedurer er i overensstemmelse med vejledningen for pleje og anvendelse af forsøgsdyr (National Academies Press, 8. udgave, 2011), og protokoller godkendes af Institutional Animal Care og brug Udvalg ved University of Wisconsin. Alle operationer blev udført under isofluran anæstesi (gennem indånding, flowhastighed 2 ml / min), og der blev gjort alt for at minimere dyrenes lidelser. Dyrene blev aflivet i et kammer efterhånden fyldt med CO 2. 1. In...

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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>

Proceduren Tråden skade er gældende for alle musestammer, så længe deres anatomiske strukturer er ens. 4 I dette papir, anvendte vi C57BL / 6-mus med en alder på 12-16 uger. Som vi har lært fra vores indledende undersøgelser, lårarterierne af mus yngre end 10 uger er ofte så små, at wire indsættelse er ganske udfordrende. På den anden side, wire indsættelse i mus ældre end 16 uger er teknisk lettere, men har tendens til at resultere i mere variabel neointimal hyperplasi. Hunmus tendens til at p?...

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

Kardiovaskulær sygdom forårsaget af aterosklerose er den førende dødsårsag i den udviklede verden. Indsnævring af karlumenet grund af aterosklerotisk plaque udvikling eller bristning af etablerede plaques, afbryder normal blodgennemstrømning fører til forskellige følgesygdomme såsom myokardieinfarkt og slagtilfælde. I klinikken endovaskulære procedurer, såsom ballonudvidelse er almindeligt udført for at genåbne lumen. Men disse behandlinger uundgåeligt beskadige karvæggen samt det vaskulære endotel, udløser en overdreven healing reaktion og udvikling af en neointimal plak, der strækker sig ind i hulrummet forårsager fartøj restenose (re-forsnævring). Restenose fortsat en væsentlig årsag til svigt af endovaskulære behandlinger for åreforkalkning. Således prækliniske dyremodeller for restenose er af vital betydning for at undersøge patofysiologiske mekanismer samt translationel tilgange til vaskulære indgreb. Blandt flere murine experimental modeller er lårarterien wire skade bredt accepteret som den mest egnede til studier af post-angioplastik restenose, fordi det ligner angioplastiproceduren der skader både endotel og karvæggen. Men mange forskere har svært ved at udnytte denne model på grund af sin høje grad af tekniske vanskeligheder. Dette skyldes primært en metaltråd skal indsættes i den femorale arterie, der er ca. tre gange tyndere end wiren, for at generere tilstrækkelig skade til at inducere fremtrædende neointima. Her beskriver vi de vigtigste kirurgiske detaljer til effektivt at overvinde de store tekniske vanskeligheder ved denne model. Ved at følge de præsenterede procedurer udfører musen lårarterien wire skade bliver lettere. Når bekendt, kan hele proceduren være afsluttet inden for 20 min.

Fire uger efter operationen, indsamles wire-sårede femoralarterie og gøre en paraffin blok prøve at analysere neointimadannelse. Fremkald generel anæstesi som beskrevet ovenfor. Åbn brystet straks og indsætte en 20-gauge butterfly nålen til den venstre ventrikel. Slut linje til en infusion flaske. Udfør perfusion fiksering via dråbeinfusion PBS efterfulgt af 4% paraformaldehyd (som regel 10-20 ml hver). Infusionen flasken placeres ca. 140 cm højere end hjertet niveau, så dyret perfuseres ved fysiolog...

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

Musen femorale arterie wire skade model af restenose er teknisk udfordrende. I denne protokol viser vi de vigtigste tekniske detaljer afgørende for en vellykket udførelse af wire skade at fremkalde ensartet neointima for studier af restenose.

En murin model af arteriel restenose: Tekniske aspekter af Femoral Wire Skade

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