<meta charset="utf8"></head><body>חקירת המנגנונים המולקולריים העומדים בבסיס מפרצת אבי העורקים הבטני

<ol>
	<li>Chaikof, E. L., 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=The+Society+for+Vascular+Surgery+practices+guidelines+on+the+care+of+patients+with+an+abdominal+aortic+aneurysm.">The Society for Vascular Surgery practices guidelines on the care of patients with an abdominal aortic aneurysm.</a> J Vasc Surg. 67 (1), 2-77 (2018).</li><li>Johnston, K. W., 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=Suggested+standards+for+reporting+on+arterial+aneurysms.+Subcommittee+on+reporting+standards+for+arterial+aneurysms,+ad+hoc+committee+on+reporting+standards,+society+for+vascular+surgery+and+north+American+chapter,+international+society+for+cardiovascular+surgery.">Suggested standards for reporting on arterial aneurysms. Subcommittee on reporting standards for arterial aneurysms, ad hoc committee on reporting standards, society for vascular surgery and north American chapter, international society for cardiovascular surgery.</a> J Vasc Surg. 13 (3), 452-458 (1991).</li><li>Bown, M. J., Sutton, A. J., Bell, P. R. F., Sayers, R. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+meta-analysis+of+50+years+of+ruptured+abdominal+aortic+aneurysm+repair.">A meta-analysis of 50 years of ruptured abdominal aortic aneurysm repair.</a> Br J Surg. 89 (6), 714-730 (2002).</li><li>Erbel, R., 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=Esc+guidelines+on+the+diagnosis+and+treatment+of+aortic+diseases:+Document+covering+acute+and+chronic+aortic+diseases+of+the+thoracic+and+abdominal+aorta+of+the+adult.+The+task+force+for+the+diagnosis+and+treatment+of+aortic+diseases+of+the+European+Society+of+Cardiology+(ESC).">Esc guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The task force for the diagnosis and treatment of aortic diseases of the European Society of Cardiology (ESC).</a> Eur Heart J. 35 (41), 2873-2926 (2014).</li><li>Wanhainen, A., 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=Editor's+choice+-+European+Society+for+Vascular+Surgery+(ESVS)+2019+clinical+practice+guidelines+on+the+management+of+abdominal+aorto-iliac+artery+aneurysms.">Editor's choice - European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.</a> Eur J Vasc Endovasc Surg. 57 (1), 8-93 (2019).</li><li>Veith, F. J., Ohki, T., Lipsitz, E. C., Suggs, W. D., Cynamon, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+ruptured+abdominal+aneurysms+with+stent+grafts:+A+new+gold+standard.">Treatment of ruptured abdominal aneurysms with stent grafts: A new gold standard.</a> Semin Vasc Surg. 16 (2), 171-175 (2003).</li><li>Golledge, J., Thanigaimani, S., Powell, J. T., Tsao, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathogenesis+and+management+of+abdominal+aortic+aneurysm.">Pathogenesis and management of abdominal aortic aneurysm.</a> Eur Heart J. 44 (29), 2682-2697 (2023).</li><li>Wanhainen, A., 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=Editor's+choice+--+European+Society+for+Vascular+Surgery+(ESVS)+2024+clinical+practice+guidelines+on+the+management+of+abdominal+aorto-iliac+artery+aneurysms.">Editor's choice -- European Society for Vascular Surgery (ESVS) 2024 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.</a> Eur J Vasc Endovasc Surg. 67 (2), 192-331 (2024).</li><li>Golledge, J., 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=Lack+of+an+effective+drug+therapy+for+abdominal+aortic+aneurysm.">Lack of an effective drug therapy for abdominal aortic aneurysm.</a> J Intern Med. 288 (1), 6-22 (2020).</li><li>Li, R., Liu, Y., Jiang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Research+advances+in+drug+therapy+for+abdominal+aortic+aneurysms+over+the+past+five+years:+An+updated+narrative+review.">Research advances in drug therapy for abdominal aortic aneurysms over the past five years: An updated narrative review.</a> Int J Cardiol. 372, 93-100 (2023).</li><li>Lysgaard Poulsen, J., Stubbe, J., Lindholt, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+used+to+explore+abdominal+aortic+aneurysms:+A+systematic+review.">Animal models used to explore abdominal aortic aneurysms: A systematic review.</a> Eur J Vasc Endovasc Surg. 52 (4), 487-499 (2016).</li><li>S&#233;n&#233;maud, J., 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=Translational+relevance+and+recent+advances+of+animal+models+of+abdominal+aortic+aneurysm.">Translational relevance and recent advances of animal models of abdominal aortic aneurysm.</a> Arterioscler Thromb Vasc Biol. 37 (3), 401-410 (2017).</li><li>Patelis, 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=Animal+models+in+the+research+of+abdominal+aortic+aneurysm+development.">Animal models in the research of abdominal aortic aneurysm development.</a> Physiol Res. 66 (6), 899-915 (2017).</li><li>Golledge, J., Krishna, S. M., Wang, Y. <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+for+abdominal+aortic+aneurysm.">Mouse models for abdominal aortic aneurysm.</a> Br J Pharmacol. 179 (5), 792-810 (2022).</li><li>Deng, G. G., 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=Urokinase-type+plasminogen+activator+plays+a+critical+role+in+angiotensin+II-induced+abdominal+aortic+aneurysm.">Urokinase-type plasminogen activator plays a critical role in angiotensin II-induced abdominal aortic aneurysm.</a> Circ Res. 92 (5), 510-517 (2003).</li><li>Gertz, S. D., Kurgan, A., Eisenberg, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aneurysm+of+the+rabbit+common+carotid+artery+induced+by+periarterial+application+of+calcium+chloride+in+vivo.">Aneurysm of the rabbit common carotid artery induced by periarterial application of calcium chloride in vivo.</a> J Clin Invest. 81 (3), 649-656 (1988).</li><li>Chiou, A. C., Chiu, B., Pearce, W. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Murine+aortic+aneurysm+produced+by+periarterial+application+of+calcium+chloride.">Murine aortic aneurysm produced by periarterial application of calcium chloride.</a> J Surg Res. 99 (2), 371-376 (2001).</li><li>Zhang, S., Cai, Z., Zhang, X., Ma, T., Kong, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+calcium+phosphate-induced+mouse+abdominal+aortic+aneurysm+model.">A calcium phosphate-induced mouse abdominal aortic aneurysm model.</a> J Vis Exp. (189), e64173 (2022).</li><li>Isenburg, J. C., Simionescu, D. T., Starcher, B. C., Vyavahare, N. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Elastin+stabilization+for+treatment+of+abdominal+aortic+aneurysms.">Elastin stabilization for treatment of abdominal aortic aneurysms.</a> Circulation. 115 (13), 1729-1737 (2007).</li><li>Anidjar, S., 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=Elastase-induced+experimental+aneurysms+in+rats.">Elastase-induced experimental aneurysms in rats.</a> Circulation. 82 (3), 973-981 (1990).</li><li>Bhamidipati, C. 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=Development+of+a+novel+murine+model+of+aortic+aneurysms+using+peri-adventitial+elastase.">Development of a novel murine model of aortic aneurysms using peri-adventitial elastase.</a> Surgery. 152 (2), 238-246 (2012).</li><li>Xue, C., Zhao, G., Zhao, Y., Chen, Y. E., Zhang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+abdominal+aortic+aneurysm+model+induced+by+perivascular+application+of+elastase.">Mouse abdominal aortic aneurysm model induced by perivascular application of elastase.</a> J Vis Exp. (180), e63608 (2022).</li><li>Origuchi, 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=Aneurysm+induced+by+periarterial+application+of+elastase+heals+spontaneously.">Aneurysm induced by periarterial application of elastase heals spontaneously.</a> Int Angiol. 17 (2), 113-119 (1998).</li><li>Tanaka, A., Hasegawa, T., Zhi, C., Okita, Y., Okada, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+rat+model+of+abdominal+aortic+aneurysm+using+a+combination+of+intraluminal+elastase+infusion+and+extraluminal+calcium+chloride+exposure.">A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure.</a> J Vasc Surg. 50 (6), 1423-1432 (2009).</li><li>Zhu, J. X., 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=Establishment+of+a+new+abdominal+aortic+aneurysm+model+in+rats+by+a+retroperitoneal+approach.">Establishment of a new abdominal aortic aneurysm model in rats by a retroperitoneal approach.</a> Front Cardiovasc Med. 9, 808732 (2022).</li><li>Bi, Y., 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=Development+of+a+novel+rabbit+model+of+abdominal+aortic+aneurysm+via+a+combination+of+periaortic+calcium+chloride+and+elastase+incubation.">Development of a novel rabbit model of abdominal aortic aneurysm via a combination of periaortic calcium chloride and elastase incubation.</a> PLoS One. 8 (7), e68476 (2013).</li><li>Gage, G. J., Kipke, D. R., Shain, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Whole+animal+perfusion+fixation+for+rodents.">Whole animal perfusion fixation for rodents.</a> J Vis Exp. (65), e3564 (2012).</li><li>Ishida, Y., 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=Prevention+of+CaCl2-induced+aortic+inflammation+and+subsequent+aneurysm+formation+by+the+CCL3-CCR5+axis.">Prevention of CaCl2-induced aortic inflammation and subsequent aneurysm formation by the CCL3-CCR5 axis.</a> Nat Commun. 11 (1), 5994 (2020).</li><li>Economou, S. G., Taylor, C. B., Beattie, E. J., Davis, C. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persistent+experimental+aortic+aneurysms+in+dogs.">Persistent experimental aortic aneurysms in dogs.</a> Surgery. 47, 21-28 (1960).</li><li>Freestone, T., Turner, R. J., Higman, D. J., Lever, M. J., Powell, J. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+hypercholesterolemia+and+adventitial+inflammation+on+the+development+of+aortic+aneurysm+in+rabbits.">Influence of hypercholesterolemia and adventitial inflammation on the development of aortic aneurysm in rabbits.</a> Arterioscler Thromb Vasc Biol. 17 (1), 10-17 (1997).</li><li>Carsten, C. G., 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=Elastase+is+not+sufficient+to+induce+experimental+abdominal+aortic+aneurysms.">Elastase is not sufficient to induce experimental abdominal aortic aneurysms.</a> J Vasc Surg. 33 (6), 1255-1262 (2001).</li><li>Yue, J., Yin, L., Shen, J., Liu, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+modified+murine+abdominal+aortic+aneurysm+rupture+model+using+elastase+perfusion+and+angiotensin+II+infusion.">A modified murine abdominal aortic aneurysm rupture model using elastase perfusion and angiotensin II infusion.</a> Ann Vasc Surg. 67, 474-481 (2020).</li><li>Ailawadi, G., 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=Gender+differences+in+experimental+aortic+aneurysm+formation.">Gender differences in experimental aortic aneurysm formation.</a> Arterioscler Thromb Vasc Biol. 24 (11), 2116-2122 (2004).</li><li>Furubayashi, K., 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=The+significance+of+chymase+in+the+progression+of+abdominal+aortic+aneurysms+in+dogs.">The significance of chymase in the progression of abdominal aortic aneurysms in dogs.</a> Hypertens Res. 30 (4), 349-357 (2007).</li><li>Bi, Y., 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=Performance+of+a+modified+rabbit+model+of+abdominal+aortic+aneurysm+induced+by+topical+application+of+porcine+elastase:+5-month+follow-up+study.">Performance of a modified rabbit model of abdominal aortic aneurysm induced by topical application of porcine elastase: 5-month follow-up study.</a> Eur J Vasc Endovasc Surg. 45 (2), 145-152 (2013).</li><li>Wu, X. F., Zhang, J., Paskauskas, S., Xin, S. J., Duan, Z. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+estrogen+in+the+formation+of+experimental+abdominal+aortic+aneurysm.">The role of estrogen in the formation of experimental abdominal aortic aneurysm.</a> Am J Surg. 197 (1), 49-54 (2009).</li></ol>

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Anesthesia Machine</td>
			<td>RWD</td>
			<td>R550</td>
			<td></td>
		</tr>
		<tr>
			<td>Butorphanol</td>
			<td>Jiangsu Hengrui Pharmaceutical Co., Ltd</td>
			<td>220608BP</td>
			<td>1ml: 1mg</td>
		</tr>
		<tr>
			<td>C57BL/6JGpt Male Mice</td>
			<td>GemPharmatech</td>
			<td>N000013</td>
			<td></td>
		</tr>
		<tr>
			<td>Calcium Chloride</td>
			<td>Sigma Aldrich</td>
			<td>C4901</td>
			<td>100 g</td>
		</tr>
		<tr>
			<td>Carprofen</td>
			<td>MCE</td>
			<td>HY-B1227</td>
			<td>100 mg</td>
		</tr>
		<tr>
			<td>Chow Diet</td>
			<td>Dossy Experimental Animals Co.Ltd</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Digital Caliper</td>
			<td>Greener</td>
			<td>IP54</td>
			<td></td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>Jinhe Pharmaceutical Co.Ltd</td>
			<td>539682</td>
			<td>75%/500 mL</td>
		</tr>
		<tr>
			<td>EVG Staining Kit</td>
			<td>Solarbio</td>
			<td>G1597</td>
			<td></td>
		</tr>
		<tr>
			<td>GraphPad Prism</td>
			<td>Graphpad</td>
			<td></td>
			<td>Ver 9.0.0</td>
		</tr>
		<tr>
			<td>H&#38;E Staining Kit</td>
			<td>Servicebio</td>
			<td>G1076</td>
			<td></td>
		</tr>
		<tr>
			<td>Insulin Syringe</td>
			<td>BD</td>
			<td>2143420</td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>RWD</td>
			<td>R510-22-4</td>
			<td>100 mL</td>
		</tr>
		<tr>
			<td>Masson Staining Kit</td>
			<td>Servicebio</td>
			<td>G1006</td>
			<td></td>
		</tr>
		<tr>
			<td>Normal Saline</td>
			<td>Servicebio</td>
			<td>G4702</td>
			<td>500 mL</td>
		</tr>
		<tr>
			<td>Paraformaldehyde</td>
			<td>Biosharp</td>
			<td>BL539A</td>
			<td>4%/500 mL</td>
		</tr>
		<tr>
			<td>PBS, 1x</td>
			<td>Servicebio</td>
			<td>G4202</td>
			<td>500 mL</td>
		</tr>
		<tr>
			<td>Porcine Pancreatic Elastase</td>
			<td>Sigma Aldrich</td>
			<td>E1250</td>
			<td>100 mg</td>
		</tr>
		<tr>
			<td>Povidine Iodine</td>
			<td>Yongan Pharmaceutical Co.Ltd</td>
			<td></td>
			<td>5%/100 mg</td>
		</tr>
		<tr>
			<td>Prolene Polypropylene Suture</td>
			<td>Ethicon LLC</td>
			<td>8709H</td>
			<td></td>
		</tr>
		<tr>
			<td>Rodent Ultrasound System</td>
			<td>Fujifilm</td>
			<td>Vevo 3100LT</td>
			<td></td>
		</tr>
		<tr>
			<td>Stereo Microscope</td>
			<td>Olympus</td>
			<td>SZ61</td>
			<td></td>
		</tr>
		<tr>
			<td>Ultrasonic Couplant</td>
			<td>Keppler</td>
			<td>KL-250</td>
			<td>250 g</td>
		</tr>
	</tbody>
</table>

a mouse abdominal aortic aneurysm model by periadventitial calcium chloride and elastase infiltration

Abdominal aortic aneurysm (AAA) is defined as a diameter increase of more than 50% or a maximum aortic diameter exceeding 3 cm in the abdominal aorta. This condition poses a significant threat to life, with around a 90% mortality rate upon aneurysm rupture1,2,3. Currently, open surgical repair and endovascular aortic repair (EVAR) are the only available interventions for AAA patients4,5,6. However, there is insufficient evidence to support the effectiveness of medical treatments in inhibiting aneurysm formation or slowing the growth rate of the abdominal aorta in patients who do not have surgical indications7. Nevertheless, non-specific treatments, including persistent surveillance of maximum aneurysm diameter, blood pressure control, antiplatelet therapy, and statins, are used to reduce the risk of sudden aneurysm rupture and potential cardiovascular and neurological events as much as possible. Despite this, the role of antiplatelet medications and statins in preventing aneurysm rupture remains controversial and requires further studies5,7,8,9,10.
A stable AAA animal model is vital for investigating the pathogenesis of AAA, and numerous methods have been introduced to establish such a model11,12,13. Currently, calcium chloride (CaCl2), elastase, angiotensin II (Ang II), xenografts, and transgenic models are used in establishing rodent AAA models11,12,13. Among these, Ang II is the most commonly used in mice, while CaCl2 and elastase are also widely used in mice and rats11,12,13,14. The Ang II-induced AAA model is the sole animal model capable of inducing atherosclerosis that closely resembles human AAA pathology, which is simple and reproducible and obviates the need for laparotomy11,12,13. However, in contrast to the models induced by CaCl2 or elastase, the site of aneurysms induced by Ang II is uncertain and frequently observed in the descending aorta or suprarenal abdominal aorta, with a heightened risk of rupture11,12,13,14. The aneurysm incidence rate of the Ang II-induced AAA model in gene-deficient mice can be as high as 100%, while only 39% of C57BL/6 mice developed aneurysms, and the time and economic cost of obtaining gene-deficient mice are high13,15.
Initially introduced by Gertz et al., CaCl2 was utilized to induce aneurysm formation in the carotid artery and later modified by Chiou et al. to establish an AAA model in mice16,17. However, despite its ability to induce elastic fiber breakdown, vessel inflammation, and extracellular matrix degradation, CaCl2 lacks several human AAA features, including atherothrombosis, intraluminal thrombus (ILT), and aneurysm rupture12,18. In addition, the formation rate and diameter increase percentage of periaortic CaCl2 application remain unstable13,19. The initial intraluminal porcine pancreatic elastase (PPE) perfusion model for inducing AAA was developed by Anidjar et al. in 1990, followed by Bhamidipati et al.&#39;s report on periadventitial PPE infiltration in a murine model20,21. Nowadays, the majority of elastase-induced AAA animal models utilize Bhamidipati&#39;s protocol due to its feasibility and minimally invasive nature. However, it is important to note that the incidence rate and maximum diameter of AAA can vary and are generally lower than intra-aortic PPE perfusion. Moreover, aneurysms induced by periaortic application of elastase present a tendency to heal spontaneously11,12,20,21,22,23.
To address these limitations, Tanaka et al. proposed a combination approach involving intraluminal PPE perfusion and CaCl2 infiltration to establish an AAA model in rats, which yielded satisfactory results24. In addition, Zhu et al. demonstrated that the PPE + CaCl2 model offers advantages such as higher survival rates and increased aneurysm formation rates compared to both the single PPE group and the PPE + BAPN group25. This combined approach also exhibits good stability and reproducibility. Moreover, Bi et al. successfully established a rabbit AAA model via the combination of periaortic CaCl2 and elastase incubation. The average dilation ratio was 65.3% &#177; 8.9% on day 5, which further increased to 86.5% &#177; 28.7% on day 15 and significantly escalated to 203.6% &#177; 39.1% on day 3026. However, there is currently no existing literature reporting the induction of AAA in rodents by combining periaortic CaCl2 and elastase application.
This manuscript presents a standard protocol for establishing a murine AAA model through the combined use of periadventitial CaCl2 and elastase infiltration. The subsequent sections provide detailed surgical procedures and present representative results of the murine AAA model.

<meta charset="utf8"></head><body>מחבר זרקור: פיתוח ואפיון מודל עכברי למפרצת אבי העורקים הבטני

מודל מפרצת אבי העורקים הבטני של עכבר על ידי Periadventitial סידן כלורי והסננת אלסטאז

This study presents a protocol for establishing a mouse abdominal aortic aneurysm model using calcium chloride and porcine pancreatic elastase, which can be used to investigate the pathophysiological mechanism under abdominal aortic aneurysm. Our protocol combines advantages of periadventitial PPE and the calcium chloride infiltration, which is a safe, stable, and reproducible mouse AAA model, demonstrating a high incidence rate of AAA, significant dilation of abdominal aorta, and pathophysiological changes resembling those observed in human AAA. In future, our research team is committed to dedicated engagement in clinical and basic research pertaining to aortic and peripheral arterial disease, with a particular focus on investigating the pathogenesis of these conditions and the development of novel therapeutic approaches.

Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with high mortality rates. It is characterized by the permanent dilation of the ...

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JoVE Journal

Medicine

A Mouse Abdominal Aortic Aneurysm Model by Periadventitial Calcium Chloride and Elastase Infiltration

444 Views.  Sichuan University. מחקר זה מציג פרוטוקול לביסוס מודל מפרצת אבי העורקים הבטני של עכבר באמצעות סידן כלורי ואלסטאז לבלב חזירי, אשר ניתן להשתמש בו כדי לחקור את המנגנון הפתופיזיולוגי תחת מפרצת אבי העורקים הבטני. הפרוטוקול שלנו משלב יתרונות של PPE פריאדוונטיטיאלי וחדירת סידן כלו?...

Video: מחבר זרקור: פיתוח ואפיון מודל עכברי למפרצת אבי העורקים הבטני

Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with high mortality rates. It is characterized by the permanent dilation of the abdominal aorta with at least a 50% increase in arterial diameter. Various animal models of AAA have been introduced to mimic the pathophysiological changes and study the underlying mechanisms of AAA. Among these models, the calcium chloride (CaCl2)- and elastase-induced AAA models are commonly used in mice. However, these methods have certain limitations. Traditional intraluminal porcine pancreatic elastase (PPE) perfusion is associated with high technical difficulty and a high rupture rate, while periadventitial administration of PPE yields inconsistent results. In addition, the CaCl2-induced AAA model lacks human AAA features, such as atherothrombosis and aneurysm rupture. Therefore, the combined application of CaCl2 and PPE has been proposed as an approach to enhance success rates and induce greater diameter increases in AAA animal models. This manuscript presents a comprehensive protocol for establishing a mouse AAA model through periaortic infiltration of PPE and CaCl2 in the infrarenal segment of the abdominal aorta. By following this protocol, we can achieve an AAA formation rate of approximately 90% with technical simplicity and reproducibility. Further ultrasound and histological experiments confirm that this model effectively replicates the morphological and pathological changes observed in human AAA.

This manuscript presents a protocol for establishing a mouse abdominal aortic aneurysm model using calcium chloride and elastase, combining the advantages of previous modeling methods. This model can be utilized to investigate the pathophysiological mechanisms underlying abdominal aortic aneurysms.

Surgical Induction and Evaluation of Abdominal Aortic Aneurysm in Mice

To begin, place the anesthetized mouse in a supine position on the heating pad. After shaving and disinfection, place the mouse under the stereo microscope. Using scissors, make a longitudinal incision of approximately 2 to 2.5 centimeters along the midline of the abdomen.Enter the peritoneal cavity through the linea alba using the transabdominal approach. Place a retractor to expose the peritoneal cavity. Pack the intestines and colon into the right half of the abdomen using normal saline soaked gauze.Perform blunt separation of connective and adipose tissue adjacent to the infrarenal abdominal aorta and inferior vena cava using forceps and cotton swabs. Gently dissect the abdominal aorta and expose the gap between the abdominal aorta and the overlying psoas major. Insert the sterilized cotton pad strips into the gap without damaging the lumbar artery or vein.Place the cotton balls soaked in 0.9 molar calcium chloride on the adventitia of the abdominal aorta. After 15 minutes, remove the cotton ball. Dilute the elastase to two milligrams per milliliter with double distilled water.Using an insulin syringe, apply 50 microliters of diluted elastase to the infrarenal segment of the abdominal aorta. Wrap the cotton pad strips to cover the abdominal aorta and inferior vena cava. Cover the abdominal cavity during the process of infiltration with sterilized gauze.After 15 minutes, carefully remove the gauze and cotton pad strips. Move the intestines and colon back to their original positions. Cover the treated aorta with the mesentery and moisten the intestines with 0.9%saline to prevent adhesion.Using a 6-O non-absorbable polypropylene suture, close the muscle layer and skin. Place the mouse on the heating pad of the rodent ultrasound machine. Apply ultrasonic coupling to the abdomen and measure the maximum diameter of the aneurysm and the diameter of the normal segment of the abdominal aorta.In an Excel sheet, calculate the increased percentage of the infrarenal abdominal aorta. After the examination, use a napkin to wipe off the remaining ultrasonic couplet and place the mouse on the heating pad until fully recovered. In the PPE plus calcium chloride, 91.67%of mice developed abdominal aortic aneurysm at 21 days after surgery, whereas no aneurysm formation was observed in the Sham group.The average maximum internal diameter of the infrarenal abdominal aorta was significantly larger in the PPE plus calcium chloride group compared to the Sham group. The average maximum external diameter of the infrarenal abdominal aorta was significantly larger in the PPE plus calcium chloride group compared to the Sham group. Histological examination revealed thickening of the aortic wall, inflammatory cell infiltration, extracellular matrix degradation, collagen fiber deposition, and elastic fiber breakdown in the PPE plus calcium chloride group compared to the Sham group.