A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure.
OBJECTIVE
An ideal animal model of abdominal aortic aneurysm (AAA) is of great importance for clarifying unknown complex mechanisms of the pathogenesis. We introduce a new, simple technique to create reliable AAAs that simulate human aneurysms.


METHODS
Experimental models of AAAs were created in 71 rats by means of a 20-minute application of intraluminal elastase (30 U) and extraluminal calcium chloride (0.5M) in the 1-cm segment of infrarenal abdominal aorta (group EC, n = 26). A single application of elastase (group E, n = 24) or calcium chloride (group C, n = 21) was used as control. The treated aorta in each group was measured under physiologic conditions and harvested at 1 and 4 weeks. Successful AAA formation was defined as a dilation ratio >50%. Inflammatory response, elastolytic activity, and histology in the treated aorta were evaluated among the three groups.


RESULTS
The surgical procedure in each group was similarly completed for approximate 30 minutes and performed without any technical failure or operative death. At 4 weeks, the dilation ratio and wall thickness were 94.8% +/- 9.9% and 125.4 +/- 5.6 microm in group EC, 43.3% +/- 6.3% and 149.6 +/- 6.5 microm in group E, and 10.9% +/- 4.2% and 152.9 +/- 7.2 microm in group C. The success rate of AAA formation in group EC (92.7%) was significantly higher than that in group E (25.0%) and group C (0.0%). Less elastin content in the aortic wall was observed in group EC. At 1 week, tumor necrosis factor-alpha and interleukin-1beta messenger RNA (mRNA) expressions were significantly upregulated, and CD3+ and CD11b+ cells were significantly infiltrated into the treated aorta of group EC, compared with groups E or C. Gelatinolytic activities and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were also significantly activated in group EC.


CONCLUSIONS
The rat AAA model using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure is simple and easy to perform and is highly reliable and reproducible to create a saccular aneurysm similar to human AAAs. This model could be more useful to clarify AAA pathogenesis, mechanisms, and treatment interventions in experimental researches.
Tanaka
Akiko
A
Department of Surgery, Division of Cardiovascular Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Hasegawa
Tomomi
T
Chen
Zhi
Z
Okita
Yutaka
Y
Okada
Kenji
K
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002122:Calcium Chloride / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced; D007261:Infusions, Intra-Arterial; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D010196:Pancreatic Elastase / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D039481:CD11b Antigen; D017252:CD3 Complex; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010196:Pancreatic Elastase; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; D002122:Calcium Chloride