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.

OPMERKING: Ethiek Verklaring: Alle procedures voldoen aan de Gids voor de zorg en het gebruik van proefdieren (National Academies Press, 8e editie, 2011), en de protocollen door de Institutional Animal Care en gebruik Comite aan de Universiteit van Wisconsin goedgekeurd. Alle operaties werden uitgevoerd onder isofluraan anesthesie (door inademen, debiet 2 ml / min), en alle inspanningen werden gedaan om het lijden te minimaliseren. De dieren werden gedood in een kamer geleidelijk gevuld met CO2. <p class=...

<ol>
	<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>

De draad letsel procedure voor alle muizenstammen zolang hun anatomische structuren lijken. 4 In dit document, gebruikten we mannelijke C57BL / 6 muizen met een leeftijd van 12-16 weken. Zoals we hebben geleerd van onze voorstudies, de dijbeenslagaders van muizen jonger dan 10 weken zijn vaak zo klein dat draad inbrengen is heel uitdagend. Anderzijds, draad insertie in muizen ouder dan 16 weken technisch eenvoudiger maar pleegt te leiden tot variabele neointima hyperplasie. Vrouwelijke muizen hebben de neigin...

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

Cardiovasculaire ziekte veroorzaakt door atherosclerose is de belangrijkste doodsoorzaak in de ontwikkelde wereld. Vernauwing van de lumen van het vat, door atherosclerotische plaque ontwikkeling of het scheuren van gevestigde plaques, onderbreekt normale bloedstroom leidt tot verschillende morbiditeit zoals myocardiaal infarct en beroerte. In de kliniek endovasculaire procedures zoals angioplastie worden gewoonlijk uitgevoerd om het lumen te heropenen. Echter, deze behandelingen onvermijdelijk de vaatwand en het vasculaire endotheel beschadigen triggering een overmatige genezingsrespons en de ontwikkeling van nieuwe intima plaque die zich in het lumen waardoor vat restenose (opnieuw vernauwen). Restenose is een belangrijke oorzaak van het falen van endovasculaire behandelingen voor atherosclerose. Zo preklinische diermodellen van restenose zijn van vitaal belang voor het onderzoeken van de pathofysiologische mechanismen alsook translationeel benaderingen van vasculaire interventies. Tussen verschillende muizen experimental modellen wordt femorale slagader draad letsel algemeen aanvaard als het meest geschikt voor onderzoek van post-angioplastiek restenose omdat het lijkt op de angioplastieprocedure dat zowel endotheel en vaatwand verwondt. Veel onderzoekers hebben moeite gebruikmaking dit model door de hoge technische moeilijkheidsgraad. Dit komt vooral omdat een metalen draad moet worden ingebracht in de femorale slagader, die ongeveer drie maal dunner dan de draad voldoende schade genereren prominente neointima induceren. Hier beschrijven we de essentiële chirurgische gegevens om effectief het overwinnen van de grote technische moeilijkheden van dit model. Door het volgen van de gepresenteerde procedures, het uitvoeren van de muis dijbeenslagader draad letsel wordt makkelijker. Eenmaal vertrouwd, kan de hele procedure worden voltooid binnen 20 min.

Vier weken na de operatie, oogsten de draad gewonden dijbeenslagader en maak een paraffineblok monster tot het neointimavorming analyseren. Laten algemene anesthesie zoals hierboven beschreven. Open de kist onmiddellijk en plaats een 20-gauge vleugelnaald op de linker hartkamer. Sluit de lijn aan een infuus fles. Voer perfusiefixatie via druppelinfuus PBS gevolgd door 4% paraformaldehyde (meestal 10-20 ml elk). De infusie fles is ongeveer 140 cm hoger geplaatst dan de hoogte van het hart, zodat het dier wordt d...

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

De muis dijbeenslagader draad letsel model van restenose is technisch uitdagend. In dit protocol laten we de belangrijkste technische gegevens van essentieel belang voor het succesvol uitvoeren van draad letsel aan consistente neointima voor studies van restenose induceren.

Een muizenmodel van slagaderrestenose: technische aspecten van Femorale Wire Injury

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